Skip to main content
Top
Published in: Molecular Autism 1/2020

01-12-2020 | Autism Spectrum Disorder | Review

Human in vitro models for understanding mechanisms of autism spectrum disorder

Authors: Aaron Gordon, Daniel H. Geschwind

Published in: Molecular Autism | Issue 1/2020

Login to get access

Abstract

Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled.
Literature
1.
go back to reference Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51(3):431–44.PubMedPubMedCentralCrossRef Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, et al. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019;51(3):431–44.PubMedPubMedCentralCrossRef
2.
go back to reference Parikshak NN, Luo R, Zhang A, Won H, Lowe JK, Chandran V, et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell. 2013;155(5):1008–21.PubMedPubMedCentralCrossRef Parikshak NN, Luo R, Zhang A, Won H, Lowe JK, Chandran V, et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell. 2013;155(5):1008–21.PubMedPubMedCentralCrossRef
3.
go back to reference Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell. 2013;155(5):997–1007.PubMedPubMedCentralCrossRef Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell. 2013;155(5):997–1007.PubMedPubMedCentralCrossRef
4.
go back to reference Ben-David E, Shifman S. Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism. Mol Psychiatry. 2013;18(10):1054–6.PubMedCrossRef Ben-David E, Shifman S. Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism. Mol Psychiatry. 2013;18(10):1054–6.PubMedCrossRef
5.
go back to reference Walker RL, Ramaswami G, Hartl C, Mancuso N, Gandal MJ, de la Torre-Ubieta L, et al. Genetic control of expression and splicing in developing human brain informs disease mechanisms. Cell. 2019;179(3):750–71.e22.PubMedCrossRefPubMedCentral Walker RL, Ramaswami G, Hartl C, Mancuso N, Gandal MJ, de la Torre-Ubieta L, et al. Genetic control of expression and splicing in developing human brain informs disease mechanisms. Cell. 2019;179(3):750–71.e22.PubMedCrossRefPubMedCentral
6.
go back to reference Won H, Huang J, Opland CK, Hartl CL, Geschwind DH. Human evolved regulatory elements modulate genes involved in cortical expansion and neurodevelopmental disease susceptibility. Nat Commun. 2019;10(1):2396.PubMedPubMedCentralCrossRef Won H, Huang J, Opland CK, Hartl CL, Geschwind DH. Human evolved regulatory elements modulate genes involved in cortical expansion and neurodevelopmental disease susceptibility. Nat Commun. 2019;10(1):2396.PubMedPubMedCentralCrossRef
7.
go back to reference Chen JA, Peñagarikano O, Belgard TG, Swarup V, Geschwind DH. The emerging picture of autism spectrum disorder: genetics and pathology. Annu Rev Pathol. 2015;10(1):111–44.PubMedCrossRef Chen JA, Peñagarikano O, Belgard TG, Swarup V, Geschwind DH. The emerging picture of autism spectrum disorder: genetics and pathology. Annu Rev Pathol. 2015;10(1):111–44.PubMedCrossRef
8.
go back to reference Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017;542(7641):348–51.PubMedPubMedCentralCrossRef Hazlett HC, Gu H, Munsell BC, Kim SH, Styner M, Wolff JJ, et al. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017;542(7641):348–51.PubMedPubMedCentralCrossRef
9.
go back to reference Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309(16):1696–703.PubMedPubMedCentralCrossRef Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013;309(16):1696–703.PubMedPubMedCentralCrossRef
10.
go back to reference Croen LA, Qian Y, Ashwood P, Zerbo O, Schendel D, Pinto-Martin J, et al. Infection and fever in pregnancy and autism spectrum disorders: findings from the study to explore early development. Autism Res. 2019;12(10):1551–61.PubMedCrossRefPubMedCentral Croen LA, Qian Y, Ashwood P, Zerbo O, Schendel D, Pinto-Martin J, et al. Infection and fever in pregnancy and autism spectrum disorders: findings from the study to explore early development. Autism Res. 2019;12(10):1551–61.PubMedCrossRefPubMedCentral
11.
go back to reference Slawinski BL, Talge N, Ingersoll B, Smith A, Glazier A, Kerver J, et al. Maternal cytomegalovirus sero-positivity and autism symptoms in children. Am J Reprod Immunol. 2018;79(5):e12840.PubMedPubMedCentralCrossRef Slawinski BL, Talge N, Ingersoll B, Smith A, Glazier A, Kerver J, et al. Maternal cytomegalovirus sero-positivity and autism symptoms in children. Am J Reprod Immunol. 2018;79(5):e12840.PubMedPubMedCentralCrossRef
12.
go back to reference de la Torre-Ubieta L, Stein JL, Won H, Opland CK, Liang D, Lu D, et al. The Dynamic landscape of open chromatin during human cortical neurogenesis. Cell. 2018;172(1-2):289–304 e18.PubMedPubMedCentralCrossRef de la Torre-Ubieta L, Stein JL, Won H, Opland CK, Liang D, Lu D, et al. The Dynamic landscape of open chromatin during human cortical neurogenesis. Cell. 2018;172(1-2):289–304 e18.PubMedPubMedCentralCrossRef
13.
go back to reference Won H, de la Torre-Ubieta L, Stein JL, Parikshak NN, Huang J, Opland CK, et al. Chromosome conformation elucidates regulatory relationships in developing human brain. Nature. 2016;538(7626):523–7.PubMedPubMedCentralCrossRef Won H, de la Torre-Ubieta L, Stein JL, Parikshak NN, Huang J, Opland CK, et al. Chromosome conformation elucidates regulatory relationships in developing human brain. Nature. 2016;538(7626):523–7.PubMedPubMedCentralCrossRef
14.
go back to reference Birnbaum R, Weinberger DR. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat Rev Neurosci. 2017;18(12):727–40.PubMedCrossRef Birnbaum R, Weinberger DR. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat Rev Neurosci. 2017;18(12):727–40.PubMedCrossRef
15.
go back to reference Clifton NE, Hannon E, Harwood JC, Florio AD, Thomas KL, Holmans PA, et al. Dynamic expression of genes associated with schizophrenia and bipolar disorder across development. Translat Psychiatry. 2019;9(1):1–9.CrossRef Clifton NE, Hannon E, Harwood JC, Florio AD, Thomas KL, Holmans PA, et al. Dynamic expression of genes associated with schizophrenia and bipolar disorder across development. Translat Psychiatry. 2019;9(1):1–9.CrossRef
16.
go back to reference Schork AJ, Won H, Appadurai V, Nudel R, Gandal M, Delaneau O, et al. A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment. Nat Neurosci. 2019;22(3):353–61.PubMedPubMedCentralCrossRef Schork AJ, Won H, Appadurai V, Nudel R, Gandal M, Delaneau O, et al. A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment. Nat Neurosci. 2019;22(3):353–61.PubMedPubMedCentralCrossRef
17.
go back to reference Qiu S, Aldinger KA, Levitt P. Modeling of autism genetic variations in mice: focusing on synaptic and microcircuit dysfunctions. Dev Neurosci. 2012;34(2-3):88–100.PubMedCrossRef Qiu S, Aldinger KA, Levitt P. Modeling of autism genetic variations in mice: focusing on synaptic and microcircuit dysfunctions. Dev Neurosci. 2012;34(2-3):88–100.PubMedCrossRef
20.
go back to reference de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016;22(4):345–61.PubMedPubMedCentralCrossRef de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016;22(4):345–61.PubMedPubMedCentralCrossRef
21.
go back to reference Monteggia LM, Heimer H, Nestler EJ. Meeting report: can we make animal models of human mental illness? Biol Psychiatry. 2018. Monteggia LM, Heimer H, Nestler EJ. Meeting report: can we make animal models of human mental illness? Biol Psychiatry. 2018.
23.
go back to reference Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, et al. Canonical genetic signatures of the adult human brain. Nat Neurosci. 2015;18(12):1832–44.PubMedPubMedCentralCrossRef Hawrylycz M, Miller JA, Menon V, Feng D, Dolbeare T, Guillozet-Bongaarts AL, et al. Canonical genetic signatures of the adult human brain. Nat Neurosci. 2015;18(12):1832–44.PubMedPubMedCentralCrossRef
24.
go back to reference Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, et al. Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019. Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, et al. Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019.
25.
go back to reference Khaitovich P, Muetzel B, She X, Lachmann M, Hellmann I, Dietzsch J, et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 2004;14(8):1462–73.PubMedPubMedCentralCrossRef Khaitovich P, Muetzel B, She X, Lachmann M, Hellmann I, Dietzsch J, et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 2004;14(8):1462–73.PubMedPubMedCentralCrossRef
26.
go back to reference Hardingham GE, Pruunsild P, Greenberg ME, Bading H. Lineage divergence of activity-driven transcription and evolution of cognitive ability. Nat Rev Neurosci. 2018;19(1):9–15.PubMedCrossRef Hardingham GE, Pruunsild P, Greenberg ME, Bading H. Lineage divergence of activity-driven transcription and evolution of cognitive ability. Nat Rev Neurosci. 2018;19(1):9–15.PubMedCrossRef
27.
go back to reference Doan RN, Bae BI, Cubelos B, Chang C, Hossain AA, Al-Saad S, et al. Mutations in human accelerated regions disrupt cognition and social behavior. Cell. 2016;167(2):341–54 e12.PubMedPubMedCentralCrossRef Doan RN, Bae BI, Cubelos B, Chang C, Hossain AA, Al-Saad S, et al. Mutations in human accelerated regions disrupt cognition and social behavior. Cell. 2016;167(2):341–54 e12.PubMedPubMedCentralCrossRef
28.
go back to reference Bauman MD, Schumann CM. Advances in nonhuman primate models of autism: integrating neuroscience and behavior. Exp Neurol. 2018;299(Pt A):252–65.PubMedCrossRef Bauman MD, Schumann CM. Advances in nonhuman primate models of autism: integrating neuroscience and behavior. Exp Neurol. 2018;299(Pt A):252–65.PubMedCrossRef
30.
go back to reference Zhou Y, Sharma J, Ke Q, Landman R, Yuan J, Chen H, et al. Atypical behaviour and connectivity in SHANK3-mutant macaques. Nature. 2019;570(7761):326–31.PubMedCrossRef Zhou Y, Sharma J, Ke Q, Landman R, Yuan J, Chen H, et al. Atypical behaviour and connectivity in SHANK3-mutant macaques. Nature. 2019;570(7761):326–31.PubMedCrossRef
31.
go back to reference Varghese M, Keshav N, Jacot-Descombes S, Warda T, Wicinski B, Dickstein DL, et al. Autism spectrum disorder: neuropathology and animal models. Acta Neuropathol. 2017;134(4):537–66.PubMedPubMedCentralCrossRef Varghese M, Keshav N, Jacot-Descombes S, Warda T, Wicinski B, Dickstein DL, et al. Autism spectrum disorder: neuropathology and animal models. Acta Neuropathol. 2017;134(4):537–66.PubMedPubMedCentralCrossRef
32.
go back to reference Amin ND, Paşca SP. Building models of brain disorders with three-dimensional organoids. Neuron. 2018;100(2):389–405.PubMedCrossRef Amin ND, Paşca SP. Building models of brain disorders with three-dimensional organoids. Neuron. 2018;100(2):389–405.PubMedCrossRef
33.
34.
35.
go back to reference Mertens J, Reid D, Lau S, Kim Y, Gage FH. Aging in a Dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases. Annu Rev Genet. 2018;52(1):271–93.PubMedPubMedCentralCrossRef Mertens J, Reid D, Lau S, Kim Y, Gage FH. Aging in a Dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases. Annu Rev Genet. 2018;52(1):271–93.PubMedPubMedCentralCrossRef
36.
go back to reference Brown J, Quadrato G, Arlotta P. Chapter Four - Studying the brain in a dish: 3D cell culture models of human brain development and disease. In: Brivanlou AH, editor. Current Topics in Developmental Biology. Human Embryonic Stem Cells in Development: 129: Academic Press; 2018. p. 99–122. Brown J, Quadrato G, Arlotta P. Chapter Four - Studying the brain in a dish: 3D cell culture models of human brain development and disease. In: Brivanlou AH, editor. Current Topics in Developmental Biology. Human Embryonic Stem Cells in Development: 129: Academic Press; 2018. p. 99–122.
37.
go back to reference Centeno EGZ, Cimarosti H, Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol Neurodegener. 2018;13. Centeno EGZ, Cimarosti H, Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol Neurodegener. 2018;13.
38.
go back to reference Setia H, Muotri AR. Brain organoids as a model system for human neurodevelopment and disease. Semin Cell Dev Biol. 2019. Setia H, Muotri AR. Brain organoids as a model system for human neurodevelopment and disease. Semin Cell Dev Biol. 2019.
39.
go back to reference Mertens J, Marchetto MC, Bardy C, Gage FH. Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat Rev Neurosci. 2016;17(7):424–37.PubMedPubMedCentralCrossRef Mertens J, Marchetto MC, Bardy C, Gage FH. Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience. Nat Rev Neurosci. 2016;17(7):424–37.PubMedPubMedCentralCrossRef
40.
go back to reference Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, et al. A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods. 1998;85(2):141–52.PubMedCrossRef Svendsen CN, ter Borg MG, Armstrong RJ, Rosser AE, Chandran S, Ostenfeld T, et al. A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Methods. 1998;85(2):141–52.PubMedCrossRef
41.
go back to reference Stein JL, de la Torre-Ubieta L, Tian Y, Parikshak NN, Hernandez IA, Marchetto MC, et al. A quantitative framework to evaluate modeling of cortical development by neural stem cells. Neuron. 2014;83(1):69–86.PubMedPubMedCentralCrossRef Stein JL, de la Torre-Ubieta L, Tian Y, Parikshak NN, Hernandez IA, Marchetto MC, et al. A quantitative framework to evaluate modeling of cortical development by neural stem cells. Neuron. 2014;83(1):69–86.PubMedPubMedCentralCrossRef
42.
go back to reference Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463(7284):1035–41.PubMedPubMedCentralCrossRef Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463(7284):1035–41.PubMedPubMedCentralCrossRef
43.
go back to reference Tsunemoto R, Lee S, Szűcs A, Chubukov P, Sokolova I, Blanchard JW, et al. Diverse reprogramming codes for neuronal identity. Nature. 2018;557(7705):375–80.PubMedPubMedCentralCrossRef Tsunemoto R, Lee S, Szűcs A, Chubukov P, Sokolova I, Blanchard JW, et al. Diverse reprogramming codes for neuronal identity. Nature. 2018;557(7705):375–80.PubMedPubMedCentralCrossRef
44.
go back to reference Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 2015;17(6):705–18.PubMedPubMedCentralCrossRef Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 2015;17(6):705–18.PubMedPubMedCentralCrossRef
45.
go back to reference Huh CJ, Zhang B, Victor MB, Dahiya S, Batista LF, Horvath S, et al. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. Elife. 2016;5. Huh CJ, Zhang B, Victor MB, Dahiya S, Batista LF, Horvath S, et al. Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. Elife. 2016;5.
47.
go back to reference Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359–67.PubMedCrossRef Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359–67.PubMedCrossRef
48.
go back to reference Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, et al. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell. 2011;9(2):113–8.PubMedPubMedCentralCrossRef Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, et al. Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions. Cell Stem Cell. 2011;9(2):113–8.PubMedPubMedCentralCrossRef
49.
go back to reference Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, et al. Induction of human neuronal cells by defined transcription factors. Nature. 2011;476(7359):220–3.PubMedPubMedCentralCrossRef Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, et al. Induction of human neuronal cells by defined transcription factors. Nature. 2011;476(7359):220–3.PubMedPubMedCentralCrossRef
50.
go back to reference Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011;476(7359):228–31.PubMedPubMedCentralCrossRef Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature. 2011;476(7359):228–31.PubMedPubMedCentralCrossRef
51.
go back to reference Ladewig J, Mertens J, Kesavan J, Doerr J, Poppe D, Glaue F, et al. Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat Methods. 2012;9(6):575–8.PubMedCrossRef Ladewig J, Mertens J, Kesavan J, Doerr J, Poppe D, Glaue F, et al. Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat Methods. 2012;9(6):575–8.PubMedCrossRef
52.
go back to reference Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Li H, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152(1-2):82–96.PubMedPubMedCentralCrossRef Xue Y, Ouyang K, Huang J, Zhou Y, Ouyang H, Li H, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell. 2013;152(1-2):82–96.PubMedPubMedCentralCrossRef
53.
go back to reference Lau S, Rylander Ottosson D, Jakobsson J, Parmar M. Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors. Cell Rep. 2014;9(5):1673–80.PubMedCrossRef Lau S, Rylander Ottosson D, Jakobsson J, Parmar M. Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors. Cell Rep. 2014;9(5):1673–80.PubMedCrossRef
54.
go back to reference Hu W, Qiu B, Guan W, Wang Q, Wang M, Li W, et al. Direct conversion of normal and Alzheimer’s disease human fibroblasts into neuronal cells by small molecules. Cell Stem Cell. 2015;17(2):204–12.PubMedCrossRef Hu W, Qiu B, Guan W, Wang Q, Wang M, Li W, et al. Direct conversion of normal and Alzheimer’s disease human fibroblasts into neuronal cells by small molecules. Cell Stem Cell. 2015;17(2):204–12.PubMedCrossRef
55.
go back to reference Li X, Zuo X, Jing J, Ma Y, Wang J, Liu D, et al. Small-molecule-driven direct reprogramming of mouse fibroblasts into functional neurons. Cell Stem Cell. 2015;17(2):195–203.PubMedCrossRef Li X, Zuo X, Jing J, Ma Y, Wang J, Liu D, et al. Small-molecule-driven direct reprogramming of mouse fibroblasts into functional neurons. Cell Stem Cell. 2015;17(2):195–203.PubMedCrossRef
56.
go back to reference Lee SH, Jeyapalan JN, Appleby V, Mohamed Noor DA, Sottile V, Scotting PJ. Dynamic methylation and expression of Oct4 in early neural stem cells. J Anat. 2010;217(3):203–13.PubMedPubMedCentralCrossRef Lee SH, Jeyapalan JN, Appleby V, Mohamed Noor DA, Sottile V, Scotting PJ. Dynamic methylation and expression of Oct4 in early neural stem cells. J Anat. 2010;217(3):203–13.PubMedPubMedCentralCrossRef
57.
go back to reference Watanabe D, Uchiyama K, Hanaoka K. Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development. Neuroscience. 2006;142(3):727–37.PubMedCrossRef Watanabe D, Uchiyama K, Hanaoka K. Transition of mouse de novo methyltransferases expression from Dnmt3b to Dnmt3a during neural progenitor cell development. Neuroscience. 2006;142(3):727–37.PubMedCrossRef
58.
go back to reference Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.PubMedCrossRef Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.PubMedCrossRef
59.
go back to reference Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, et al. FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell. 2015;162(2):375–90.PubMedPubMedCentralCrossRef Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, et al. FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell. 2015;162(2):375–90.PubMedPubMedCentralCrossRef
60.
go back to reference Marchetto MC, Belinson H, Tian Y, Freitas BC, Fu C, Vadodaria K, et al. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Mol Psychiatry. 2017;22(6):820–35.PubMedCrossRef Marchetto MC, Belinson H, Tian Y, Freitas BC, Fu C, Vadodaria K, et al. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Mol Psychiatry. 2017;22(6):820–35.PubMedCrossRef
61.
go back to reference de Boni L, Gasparoni G, Haubenreich C, Tierling S, Schmitt I, Peitz M, et al. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling. Clin Epigenetics. 2018;10:13.PubMedPubMedCentralCrossRef de Boni L, Gasparoni G, Haubenreich C, Tierling S, Schmitt I, Peitz M, et al. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling. Clin Epigenetics. 2018;10:13.PubMedPubMedCentralCrossRef
62.
63.
go back to reference Bar S, Benvenisty N. Epigenetic aberrations in human pluripotent stem cells. EMBO J. 2019;38(12). Bar S, Benvenisty N. Epigenetic aberrations in human pluripotent stem cells. EMBO J. 2019;38(12).
64.
go back to reference Tesarova L, Simara P, Stejskal S, Koutna I. The aberrant DNA methylation profile of human induced pluripotent stem cells is connected to the reprogramming process and is normalized during in vitro culture. PLoS One. 2016;11(6):e0157974.PubMedPubMedCentralCrossRef Tesarova L, Simara P, Stejskal S, Koutna I. The aberrant DNA methylation profile of human induced pluripotent stem cells is connected to the reprogramming process and is normalized during in vitro culture. PLoS One. 2016;11(6):e0157974.PubMedPubMedCentralCrossRef
65.
go back to reference Roost MS, Slieker RC, Bialecka M, van Iperen L, Gomes Fernandes MM, He N, et al. DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells. Nat Commun. 2017;8(1):908.PubMedPubMedCentralCrossRef Roost MS, Slieker RC, Bialecka M, van Iperen L, Gomes Fernandes MM, He N, et al. DNA methylation and transcriptional trajectories during human development and reprogramming of isogenic pluripotent stem cells. Nat Commun. 2017;8(1):908.PubMedPubMedCentralCrossRef
66.
go back to reference Popp B, Krumbiegel M, Grosch J, Sommer A, Uebe S, Kohl Z, et al. Need for high-resolution genetic analysis in iPSC: results and lessons from the ForIPS consortium. Sci Rep. 2018;8(1):1–14.CrossRef Popp B, Krumbiegel M, Grosch J, Sommer A, Uebe S, Kohl Z, et al. Need for high-resolution genetic analysis in iPSC: results and lessons from the ForIPS consortium. Sci Rep. 2018;8(1):1–14.CrossRef
67.
go back to reference Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001;19(12):1129–33.PubMedCrossRef Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol. 2001;19(12):1129–33.PubMedCrossRef
68.
go back to reference Yan Y, Yang D, Zarnowska ED, Du Z, Werbel B, Valliere C, et al. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells. 2005;23(6):781–90.PubMedPubMedCentralCrossRef Yan Y, Yang D, Zarnowska ED, Du Z, Werbel B, Valliere C, et al. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells. 2005;23(6):781–90.PubMedPubMedCentralCrossRef
69.
go back to reference Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27(3):275–80.PubMedPubMedCentralCrossRef Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009;27(3):275–80.PubMedPubMedCentralCrossRef
70.
go back to reference Shi Y, Kirwan P, Livesey FJ. Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks. Nat Prot. 2012;7(10):1836–46.CrossRef Shi Y, Kirwan P, Livesey FJ. Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks. Nat Prot. 2012;7(10):1836–46.CrossRef
71.
go back to reference Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013;78(5):785–98.PubMedPubMedCentralCrossRef Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013;78(5):785–98.PubMedPubMedCentralCrossRef
72.
go back to reference Yang N, Chanda S, Marro S, Ng Y-H, Janas JA, Haag D, et al. Generation of pure GABAergic neurons by transcription factor programming. Nature Methods. 2017;14(6):621–8.PubMedPubMedCentralCrossRef Yang N, Chanda S, Marro S, Ng Y-H, Janas JA, Haag D, et al. Generation of pure GABAergic neurons by transcription factor programming. Nature Methods. 2017;14(6):621–8.PubMedPubMedCentralCrossRef
73.
go back to reference Lee CT, Bendriem RM, Wu WW, Shen RF. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J Biomed Sci. 2017;24(1):59.PubMedPubMedCentralCrossRef Lee CT, Bendriem RM, Wu WW, Shen RF. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J Biomed Sci. 2017;24(1):59.PubMedPubMedCentralCrossRef
74.
go back to reference Pasca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015;12(7):671–8.PubMedPubMedCentralCrossRef Pasca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015;12(7):671–8.PubMedPubMedCentralCrossRef
75.
go back to reference Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013;501(7467):373–9.PubMedCrossRef Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013;501(7467):373–9.PubMedCrossRef
76.
go back to reference Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell. 2016;165(5):1238–54.PubMedPubMedCentralCrossRef Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell. 2016;165(5):1238–54.PubMedPubMedCentralCrossRef
77.
go back to reference Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, et al. Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. Neuron. 2017;95(4):779–90 e6.PubMedPubMedCentralCrossRef Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, et al. Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. Neuron. 2017;95(4):779–90 e6.PubMedPubMedCentralCrossRef
78.
go back to reference Bhaduri A, Andrews MG, Mancia Leon W, Jung D, Shin D, Allen D, et al. Cell stress in cortical organoids impairs molecular subtype specification. Nature. 2020. Bhaduri A, Andrews MG, Mancia Leon W, Jung D, Shin D, Allen D, et al. Cell stress in cortical organoids impairs molecular subtype specification. Nature. 2020.
79.
go back to reference Amiri A, Coppola G, Scuderi S, Wu F, Roychowdhury T, Liu F, et al. Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science. 2018;362:6420.CrossRef Amiri A, Coppola G, Scuderi S, Wu F, Roychowdhury T, Liu F, et al. Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science. 2018;362:6420.CrossRef
80.
go back to reference Camp JG, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Brauninger M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A. 2015;112(51):15672–7.PubMedPubMedCentralCrossRef Camp JG, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Brauninger M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A. 2015;112(51):15672–7.PubMedPubMedCentralCrossRef
81.
go back to reference Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Min Yang S, Berger DR, et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature. 2017;545(7652):48–53.PubMedPubMedCentralCrossRef Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Min Yang S, Berger DR, et al. Cell diversity and network dynamics in photosensitive human brain organoids. Nature. 2017;545(7652):48–53.PubMedPubMedCentralCrossRef
82.
go back to reference Kanton S, Boyle MJ, He Z, Santel M, Weigert A, Sanchís-Calleja F, et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 2019;574(7778):418–22.PubMedCrossRef Kanton S, Boyle MJ, He Z, Santel M, Weigert A, Sanchís-Calleja F, et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 2019;574(7778):418–22.PubMedCrossRef
83.
go back to reference Pollen AA, Bhaduri A, Andrews MG, Nowakowski TJ, Meyerson OS, Mostajo-Radji MA, et al. Establishing cerebral organoids as models of human-specific brain evolution. Cell. 2019;176(4):743–56.e17.PubMedPubMedCentralCrossRef Pollen AA, Bhaduri A, Andrews MG, Nowakowski TJ, Meyerson OS, Mostajo-Radji MA, et al. Establishing cerebral organoids as models of human-specific brain evolution. Cell. 2019;176(4):743–56.e17.PubMedPubMedCentralCrossRef
84.
go back to reference Velasco S, Kedaigle AJ, Simmons SK, Nash A, Rocha M, Quadrato G, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature. 2019;1. Velasco S, Kedaigle AJ, Simmons SK, Nash A, Rocha M, Quadrato G, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature. 2019;1.
85.
go back to reference Birey F, Andersen J, Makinson CD, Islam S, Wei W, Huber N, et al. Assembly of functionally integrated human forebrain spheroids. Nature. 2017;545(7652):54–9.PubMedPubMedCentralCrossRef Birey F, Andersen J, Makinson CD, Islam S, Wei W, Huber N, et al. Assembly of functionally integrated human forebrain spheroids. Nature. 2017;545(7652):54–9.PubMedPubMedCentralCrossRef
86.
go back to reference Yoon SJ, Elahi LS, Pasca AM, Marton RM, Gordon A, Revah O, et al. Reliability of human cortical organoid generation. Nat Methods. 2019;16(1):75–8.PubMedCrossRef Yoon SJ, Elahi LS, Pasca AM, Marton RM, Gordon A, Revah O, et al. Reliability of human cortical organoid generation. Nat Methods. 2019;16(1):75–8.PubMedCrossRef
87.
go back to reference Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, et al. Fusion of regionally specified hPSC-derived organoids models human brain development and interneuron migration. Cell Stem Cell. 2017;21(3):383–98 e7.PubMedPubMedCentralCrossRef Xiang Y, Tanaka Y, Patterson B, Kang YJ, Govindaiah G, Roselaar N, et al. Fusion of regionally specified hPSC-derived organoids models human brain development and interneuron migration. Cell Stem Cell. 2017;21(3):383–98 e7.PubMedPubMedCentralCrossRef
88.
go back to reference Bagley JA, Reumann D, Bian S, Levi-Strauss J, Knoblich JA. Fused cerebral organoids model interactions between brain regions. Nat Methods. 2017;14(7):743–51.PubMedPubMedCentralCrossRef Bagley JA, Reumann D, Bian S, Levi-Strauss J, Knoblich JA. Fused cerebral organoids model interactions between brain regions. Nat Methods. 2017;14(7):743–51.PubMedPubMedCentralCrossRef
89.
go back to reference Trevino AE, Sinnott-Armstrong N, Andersen J, Yoon SJ, Huber N, Pritchard JK, et al. Chromatin accessibility dynamics in a model of human forebrain development. Science. 2020;367:6476.CrossRef Trevino AE, Sinnott-Armstrong N, Andersen J, Yoon SJ, Huber N, Pritchard JK, et al. Chromatin accessibility dynamics in a model of human forebrain development. Science. 2020;367:6476.CrossRef
91.
go back to reference Engle SJ, Blaha L, Kleiman RJ. Best practices for translational disease modeling using human iPSC-derived neurons. Neuron. 2018;100(4):783–97.PubMedCrossRef Engle SJ, Blaha L, Kleiman RJ. Best practices for translational disease modeling using human iPSC-derived neurons. Neuron. 2018;100(4):783–97.PubMedCrossRef
92.
go back to reference Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 2014;122(10):1103–9.PubMedPubMedCentralCrossRef Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 2014;122(10):1103–9.PubMedPubMedCentralCrossRef
93.
94.
go back to reference Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8(1):13.PubMedPubMedCentralCrossRef Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8(1):13.PubMedPubMedCentralCrossRef
95.
go back to reference Freitas BC, Mei A, Mendes APD, Beltrão-Braga PCB, Marchetto MC. Modeling Inflammation in autism spectrum disorders using stem cells. Front Pediatr. 2018;6:394.PubMedPubMedCentralCrossRef Freitas BC, Mei A, Mendes APD, Beltrão-Braga PCB, Marchetto MC. Modeling Inflammation in autism spectrum disorders using stem cells. Front Pediatr. 2018;6:394.PubMedPubMedCentralCrossRef
96.
go back to reference Raciti M, Ong J, Weis L, Edoff K, Battagli C, Falk A, et al. Glucocorticoids alter neuronal differentiation of human neuroepithelial-like cells by inducing long-lasting changes in the reactive oxygen species balance. Neuropharmacology. 2016;107:422–31.PubMedCrossRef Raciti M, Ong J, Weis L, Edoff K, Battagli C, Falk A, et al. Glucocorticoids alter neuronal differentiation of human neuroepithelial-like cells by inducing long-lasting changes in the reactive oxygen species balance. Neuropharmacology. 2016;107:422–31.PubMedCrossRef
97.
go back to reference Gibbs RM, Lipnick S, Bateman JW, Chen L, Cousins HC, Hubbard EG, et al. Toward precision medicine for neurological and neuropsychiatric disorders. Cell Stem Cell. 2018;23(1):21–4.PubMedCrossRef Gibbs RM, Lipnick S, Bateman JW, Chen L, Cousins HC, Hubbard EG, et al. Toward precision medicine for neurological and neuropsychiatric disorders. Cell Stem Cell. 2018;23(1):21–4.PubMedCrossRef
98.
go back to reference Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N E J Med. 2013;369(16):1502–11.CrossRef Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, et al. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N E J Med. 2013;369(16):1502–11.CrossRef
99.
go back to reference Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016;17(5):257–71.PubMedPubMedCentralCrossRef Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016;17(5):257–71.PubMedPubMedCentralCrossRef
100.
go back to reference Cummings BB, Marshall JL, Tukiainen T, Lek M, Donkervoort S, Foley AR, et al. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Sci Translat Med. 2017;9:386. Cummings BB, Marshall JL, Tukiainen T, Lek M, Donkervoort S, Foley AR, et al. Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Sci Translat Med. 2017;9:386.
101.
go back to reference Lee H, Huang AY, Wang LK, Yoon AJ, Renteria G, Eskin A, et al. Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. Genet Med. 2019. Lee H, Huang AY, Wang LK, Yoon AJ, Renteria G, Eskin A, et al. Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. Genet Med. 2019.
102.
go back to reference Frésard L, Smail C, Ferraro NM, Teran NA, Li X, Smith KS, et al. Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat Med. 2019;1. Frésard L, Smail C, Ferraro NM, Teran NA, Li X, Smith KS, et al. Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat Med. 2019;1.
104.
go back to reference Little D, Ketteler R, Gissen P, Devine MJ. Using stem cell–derived neurons in drug screening for neurological diseases. Neurobiol Aging. 2019;78:130–41.PubMedCrossRef Little D, Ketteler R, Gissen P, Devine MJ. Using stem cell–derived neurons in drug screening for neurological diseases. Neurobiol Aging. 2019;78:130–41.PubMedCrossRef
105.
go back to reference Sherman SP, Bang AG. High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons. Dis Model Mech. 2018;11:2.CrossRef Sherman SP, Bang AG. High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons. Dis Model Mech. 2018;11:2.CrossRef
106.
go back to reference Gilbert J, Man H-Y. Fundamental elements in autism: from neurogenesis and neurite growth to synaptic plasticity. Front Cell Neurosci. 2017;11. Gilbert J, Man H-Y. Fundamental elements in autism: from neurogenesis and neurite growth to synaptic plasticity. Front Cell Neurosci. 2017;11.
107.
go back to reference Kaufmann M, Schuffenhauer A, Fruh I, Klein J, Thiemeyer A, Rigo P, et al. High-throughput screening using iPSC-derived neuronal progenitors to identify compounds counteracting epigenetic gene silencing in fragile X syndrome. J Biomol Screen. 2015;20(9):1101–11.PubMedCrossRef Kaufmann M, Schuffenhauer A, Fruh I, Klein J, Thiemeyer A, Rigo P, et al. High-throughput screening using iPSC-derived neuronal progenitors to identify compounds counteracting epigenetic gene silencing in fragile X syndrome. J Biomol Screen. 2015;20(9):1101–11.PubMedCrossRef
108.
go back to reference Darville H, Poulet A, Rodet-Amsellem F, Chatrousse L, Pernelle J, Boissart C, et al. Human pluripotent stem cell-derived cortical neurons for high throughput medication screening in autism: a proof of concept study in SHANK3 haploinsufficiency syndrome. EBio Med. 2016;9:293–305. Darville H, Poulet A, Rodet-Amsellem F, Chatrousse L, Pernelle J, Boissart C, et al. Human pluripotent stem cell-derived cortical neurons for high throughput medication screening in autism: a proof of concept study in SHANK3 haploinsufficiency syndrome. EBio Med. 2016;9:293–305.
109.
go back to reference Mertens J, Wang QW, Kim Y, Yu DX, Pham S, Yang B, et al. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature. 2015;527(7576):95–9.PubMedPubMedCentralCrossRef Mertens J, Wang QW, Kim Y, Yu DX, Pham S, Yang B, et al. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature. 2015;527(7576):95–9.PubMedPubMedCentralCrossRef
110.
go back to reference Marchetto MC, Hrvoj-Mihic B, Kerman BE, Yu DX, Vadodaria KC, Linker SB, et al. Species-specific maturation profiles of human, chimpanzee and bonobo neural cells. eLife. 2019;8:e37527.PubMedPubMedCentralCrossRef Marchetto MC, Hrvoj-Mihic B, Kerman BE, Yu DX, Vadodaria KC, Linker SB, et al. Species-specific maturation profiles of human, chimpanzee and bonobo neural cells. eLife. 2019;8:e37527.PubMedPubMedCentralCrossRef
111.
go back to reference Otani T, Marchetto MC, Gage FH, Simons BD, Livesey FJ. 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell. 2016;18(4):467–80.PubMedPubMedCentralCrossRef Otani T, Marchetto MC, Gage FH, Simons BD, Livesey FJ. 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell. 2016;18(4):467–80.PubMedPubMedCentralCrossRef
112.
go back to reference DeRosa BA, El Hokayem J, Artimovich E, Garcia-Serje C, Phillips AW, Van Booven D, et al. Convergent pathways in idiopathic autism revealed by time course transcriptomic analysis of patient-derived neurons. Sci Rep. 2018;8(1):8423.PubMedPubMedCentralCrossRef DeRosa BA, El Hokayem J, Artimovich E, Garcia-Serje C, Phillips AW, Van Booven D, et al. Convergent pathways in idiopathic autism revealed by time course transcriptomic analysis of patient-derived neurons. Sci Rep. 2018;8(1):8423.PubMedPubMedCentralCrossRef
113.
go back to reference Griesi-Oliveira K, Suzuki AM, Alves AY, Mafra A, Yamamoto GL, Ezquina S, et al. Actin cytoskeleton dynamics in stem cells from autistic individuals. Sci Rep. 2018;8(1):11138.PubMedPubMedCentralCrossRef Griesi-Oliveira K, Suzuki AM, Alves AY, Mafra A, Yamamoto GL, Ezquina S, et al. Actin cytoskeleton dynamics in stem cells from autistic individuals. Sci Rep. 2018;8(1):11138.PubMedPubMedCentralCrossRef
114.
go back to reference Schafer ST, Paquola ACM, Stern S, Gosselin D, Ku M, Pena M, et al. Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons. Nat Neurosci. 2019;22(2):243–55.PubMedPubMedCentralCrossRef Schafer ST, Paquola ACM, Stern S, Gosselin D, Ku M, Pena M, et al. Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons. Nat Neurosci. 2019;22(2):243–55.PubMedPubMedCentralCrossRef
115.
go back to reference Liu X, Campanac E, Cheung HH, Ziats MN, Canterel-Thouennon L, Raygada M, et al. Idiopathic autism: cellular and molecular phenotypes in pluripotent stem cell-derived neurons. Mol Neurobiol. 2017;54(6):4507–23.PubMedCrossRef Liu X, Campanac E, Cheung HH, Ziats MN, Canterel-Thouennon L, Raygada M, et al. Idiopathic autism: cellular and molecular phenotypes in pluripotent stem cell-derived neurons. Mol Neurobiol. 2017;54(6):4507–23.PubMedCrossRef
116.
go back to reference Russo FB, Freitas BC, Pignatari GC, Fernandes IR, Sebat J, Muotri AR, et al. Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells. Biological Psychiatry. 2018;83(7):569–78.PubMedCrossRef Russo FB, Freitas BC, Pignatari GC, Fernandes IR, Sebat J, Muotri AR, et al. Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells. Biological Psychiatry. 2018;83(7):569–78.PubMedCrossRef
117.
go back to reference Adhya D, Swarup V, Nagy R, Shum C, Nowosiad P, Jozwik KM, et al. Atypical neurogenesis and excitatory-inhibitory progenitor generation in induced pluripotent stem cell (iPSC) from autistic individuals. bioRxiv. 2019;349415. Adhya D, Swarup V, Nagy R, Shum C, Nowosiad P, Jozwik KM, et al. Atypical neurogenesis and excitatory-inhibitory progenitor generation in induced pluripotent stem cell (iPSC) from autistic individuals. bioRxiv. 2019;349415.
118.
go back to reference Moore D, Meays BM, Madduri LSV, Shahjin F, Chand S, Niu M, et al. Downregulation of an evolutionary young miR-1290 in an iPSC-derived neural stem cell model of autism spectrum disorder. Stem Cells Int. 2019;2019:8710180.PubMedPubMedCentral Moore D, Meays BM, Madduri LSV, Shahjin F, Chand S, Niu M, et al. Downregulation of an evolutionary young miR-1290 in an iPSC-derived neural stem cell model of autism spectrum disorder. Stem Cells Int. 2019;2019:8710180.PubMedPubMedCentral
119.
go back to reference Wang M, Wei PC, Lim CK, Gallina IS, Marshall S, Marchetto MC, et al. Increased neural progenitor proliferation in a hiPSC model of autism induces replication stress-associated genome instability. Cell Stem Cell. 2020;26(2):221–33 e6.PubMedCrossRefPubMedCentral Wang M, Wei PC, Lim CK, Gallina IS, Marshall S, Marchetto MC, et al. Increased neural progenitor proliferation in a hiPSC model of autism induces replication stress-associated genome instability. Cell Stem Cell. 2020;26(2):221–33 e6.PubMedCrossRefPubMedCentral
120.
go back to reference Griesi-Oliveira K, Fogo MS, Pinto BGG, Alves AY, Suzuki AM, Morales AG, et al. Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder. Mol Psychiatry. 2020. Griesi-Oliveira K, Fogo MS, Pinto BGG, Alves AY, Suzuki AM, Morales AG, et al. Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder. Mol Psychiatry. 2020.
121.
go back to reference Fink JJ, Robinson TM, Germain ND, Sirois CL, Bolduc KA, Ward AJ, et al. Disrupted neuronal maturation in Angelman syndrome-derived induced pluripotent stem cells. Nat Commun. 2017;8:15038.PubMedPubMedCentralCrossRef Fink JJ, Robinson TM, Germain ND, Sirois CL, Bolduc KA, Ward AJ, et al. Disrupted neuronal maturation in Angelman syndrome-derived induced pluripotent stem cells. Nat Commun. 2017;8:15038.PubMedPubMedCentralCrossRef
122.
go back to reference Fink JJ, Schreiner JD, Bloom JE, Baker DS, Robinson TM, Lieberman R, et al. Hyperexcitable phenotypes in iPSC-derived neurons from patients with 15q11-q13 duplication syndrome, a genetic form of autism. bioRxiv. 2018;286336. Fink JJ, Schreiner JD, Bloom JE, Baker DS, Robinson TM, Lieberman R, et al. Hyperexcitable phenotypes in iPSC-derived neurons from patients with 15q11-q13 duplication syndrome, a genetic form of autism. bioRxiv. 2018;286336.
123.
go back to reference Lin M, Lachman HM, Zheng D. Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders. Mol Cell Neurosci. 2016;73:32–42.PubMedCrossRef Lin M, Lachman HM, Zheng D. Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders. Mol Cell Neurosci. 2016;73:32–42.PubMedCrossRef
124.
go back to reference Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, et al. Analysis of induced pluripotent stem cells carrying 22q11.2 deletion. Transl Psychiatry. 2016;6(11):e934.PubMedPubMedCentralCrossRef Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, et al. Analysis of induced pluripotent stem cells carrying 22q11.2 deletion. Transl Psychiatry. 2016;6(11):e934.PubMedPubMedCentralCrossRef
125.
go back to reference Deshpande A, Yadav S, Dao DQ, Wu ZY, Hokanson KC, Cahill MK, et al. Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder. Cell Rep. 2017;21(10):2678–87.PubMedPubMedCentralCrossRef Deshpande A, Yadav S, Dao DQ, Wu ZY, Hokanson KC, Cahill MK, et al. Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder. Cell Rep. 2017;21(10):2678–87.PubMedPubMedCentralCrossRef
126.
go back to reference Gillentine MA, Yin J, Bajic A, Zhang P, Cummock S, Kim JJ, et al. Functional consequences of CHRNA7 copy-number alterations in induced pluripotent stem cells and neural progenitor cells. Am J Hum Genet. 2017;101(6):874–87.PubMedPubMedCentralCrossRef Gillentine MA, Yin J, Bajic A, Zhang P, Cummock S, Kim JJ, et al. Functional consequences of CHRNA7 copy-number alterations in induced pluripotent stem cells and neural progenitor cells. Am J Hum Genet. 2017;101(6):874–87.PubMedPubMedCentralCrossRef
127.
go back to reference Yi F, Danko T, Botelho SC, Patzke C, Pak C, Wernig M, et al. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Science. 2016;352(6286):aaf2669.PubMedPubMedCentralCrossRef Yi F, Danko T, Botelho SC, Patzke C, Pak C, Wernig M, et al. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Science. 2016;352(6286):aaf2669.PubMedPubMedCentralCrossRef
128.
go back to reference Kathuria A, Nowosiad P, Jagasia R, Aigner S, Taylor RD, Andreae LC, et al. Stem cell-derived neurons from autistic individuals with SHANK3 mutation show morphogenetic abnormalities during early development. Mol Psychiatry. 2018;23(3):735–46.PubMedCrossRef Kathuria A, Nowosiad P, Jagasia R, Aigner S, Taylor RD, Andreae LC, et al. Stem cell-derived neurons from autistic individuals with SHANK3 mutation show morphogenetic abnormalities during early development. Mol Psychiatry. 2018;23(3):735–46.PubMedCrossRef
129.
go back to reference Gouder L, Vitrac A, Goubran-Botros H, Danckaert A, Tinevez JY, Andre-Leroux G, et al. Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations. Sci Rep. 2019;9(1):94.PubMedPubMedCentralCrossRef Gouder L, Vitrac A, Goubran-Botros H, Danckaert A, Tinevez JY, Andre-Leroux G, et al. Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations. Sci Rep. 2019;9(1):94.PubMedPubMedCentralCrossRef
130.
go back to reference Huang G, Chen S, Chen X, Zheng J, Xu Z, Doostparast Torshizi A, et al. Uncovering the functional link between SHANK3 deletions and deficiency in neurodevelopment using iPSC-derived human neurons. Front Neuroanat. 2019;13:23.PubMedPubMedCentralCrossRef Huang G, Chen S, Chen X, Zheng J, Xu Z, Doostparast Torshizi A, et al. Uncovering the functional link between SHANK3 deletions and deficiency in neurodevelopment using iPSC-derived human neurons. Front Neuroanat. 2019;13:23.PubMedPubMedCentralCrossRef
131.
go back to reference Wang P, Mokhtari R, Pedrosa E, Kirschenbaum M, Bayrak C, Zheng D, et al. CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells. Mol Autism. 2017;8:11.PubMedPubMedCentralCrossRef Wang P, Mokhtari R, Pedrosa E, Kirschenbaum M, Bayrak C, Zheng D, et al. CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells. Mol Autism. 2017;8:11.PubMedPubMedCentralCrossRef
132.
go back to reference Sugathan A, Biagioli M, Golzio C, Erdin S, Blumenthal I, Manavalan P, et al. CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. PNAS. 2014;111(42):E4468–E77.PubMedCrossRefPubMedCentral Sugathan A, Biagioli M, Golzio C, Erdin S, Blumenthal I, Manavalan P, et al. CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. PNAS. 2014;111(42):E4468–E77.PubMedCrossRefPubMedCentral
133.
go back to reference Pak C, Danko T, Zhang Y, Aoto J, Anderson G, Maxeiner S, et al. Human neuropsychiatric disease modeling using conditional deletion reveals synaptic transmission defects caused by heterozygous mutations in NRXN1. Cell Stem Cell. 2015;17(3):316–28.PubMedPubMedCentralCrossRef Pak C, Danko T, Zhang Y, Aoto J, Anderson G, Maxeiner S, et al. Human neuropsychiatric disease modeling using conditional deletion reveals synaptic transmission defects caused by heterozygous mutations in NRXN1. Cell Stem Cell. 2015;17(3):316–28.PubMedPubMedCentralCrossRef
134.
go back to reference Zeng L, Zhang P, Shi L, Yamamoto V, Lu W, Wang K. Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. PLoS One. 2013;8:3.CrossRef Zeng L, Zhang P, Shi L, Yamamoto V, Lu W, Wang K. Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. PLoS One. 2013;8:3.CrossRef
135.
go back to reference Lam M, Moslem M, Bryois J, Pronk RJ, Uhlin E, Ellstrom ID, et al. Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality. Exp Cell Res. 2019;383(1):111469.PubMedCrossRef Lam M, Moslem M, Bryois J, Pronk RJ, Uhlin E, Ellstrom ID, et al. Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality. Exp Cell Res. 2019;383(1):111469.PubMedCrossRef
136.
go back to reference Avazzadeh S, McDonagh K, Reilly J, Wang Y, Boomkamp SD, McInerney V, et al. Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells. Mol Autism. 2019;10:52.PubMedPubMedCentralCrossRef Avazzadeh S, McDonagh K, Reilly J, Wang Y, Boomkamp SD, McInerney V, et al. Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells. Mol Autism. 2019;10:52.PubMedPubMedCentralCrossRef
137.
go back to reference Flaherty E, Zhu S, Barretto N, Cheng E, Deans PJM, Fernando MB, et al. Neuronal impact of patient-specific aberrant NRXN1alpha splicing. Nat Genet. 2019;51(12):1679–90.PubMedCrossRefPubMedCentral Flaherty E, Zhu S, Barretto N, Cheng E, Deans PJM, Fernando MB, et al. Neuronal impact of patient-specific aberrant NRXN1alpha splicing. Nat Genet. 2019;51(12):1679–90.PubMedCrossRefPubMedCentral
138.
go back to reference Marro SG, Chanda S, Yang N, Janas JA, Valperga G, Trotter J, et al. Neuroligin-4 regulates excitatory synaptic transmission in human neurons. Neuron. 2019;103(4):617–26 e6.PubMedCrossRefPubMedCentral Marro SG, Chanda S, Yang N, Janas JA, Valperga G, Trotter J, et al. Neuroligin-4 regulates excitatory synaptic transmission in human neurons. Neuron. 2019;103(4):617–26 e6.PubMedCrossRefPubMedCentral
139.
go back to reference Frega M, Linda K, Keller JM, Gumus-Akay G, Mossink B, van Rhijn JR, et al. Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling. Nat Commun. 2019;10(1):4928.PubMedPubMedCentralCrossRef Frega M, Linda K, Keller JM, Gumus-Akay G, Mossink B, van Rhijn JR, et al. Neuronal network dysfunction in a model for Kleefstra syndrome mediated by enhanced NMDAR signaling. Nat Commun. 2019;10(1):4928.PubMedPubMedCentralCrossRef
140.
go back to reference Ross PJ, Zhang WB, Mok RSF, Zaslavsky K, Deneault E, D’Abate L, et al. Synaptic dysfunction in human neurons with autism-associated deletions in PTCHD1-AS. Biol Psychiatry. 2020;87(2):139–49.PubMedCrossRef Ross PJ, Zhang WB, Mok RSF, Zaslavsky K, Deneault E, D’Abate L, et al. Synaptic dysfunction in human neurons with autism-associated deletions in PTCHD1-AS. Biol Psychiatry. 2020;87(2):139–49.PubMedCrossRef
141.
go back to reference Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, et al. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science. 2019;366(6472):1486–92.PubMedCrossRefPubMedCentral Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, et al. Potassium channel dysfunction in human neuronal models of Angelman syndrome. Science. 2019;366(6472):1486–92.PubMedCrossRefPubMedCentral
142.
go back to reference Paşca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A, Paşca AM, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med. 2011;17(12):1657–62.PubMedPubMedCentralCrossRef Paşca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A, Paşca AM, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med. 2011;17(12):1657–62.PubMedPubMedCentralCrossRef
143.
go back to reference Lewis EMA, Meganathan K, Baldridge D, Gontarz P, Zhang B, Bonni A, et al. Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons. Mol Autism. 2019;10:51.PubMedPubMedCentralCrossRef Lewis EMA, Meganathan K, Baldridge D, Gontarz P, Zhang B, Bonni A, et al. Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons. Mol Autism. 2019;10:51.PubMedPubMedCentralCrossRef
144.
go back to reference Lin M, Pedrosa E, Hrabovsky A, Chen J, Puliafito BR, Gilbert SR, et al. Integrative transcriptome network analysis of iPSC-derived neurons from schizophrenia and schizoaffective disorder patients with 22q11.2 deletion. BMC Syst Biol. 2016;10(1):105.PubMedPubMedCentralCrossRef Lin M, Pedrosa E, Hrabovsky A, Chen J, Puliafito BR, Gilbert SR, et al. Integrative transcriptome network analysis of iPSC-derived neurons from schizophrenia and schizoaffective disorder patients with 22q11.2 deletion. BMC Syst Biol. 2016;10(1):105.PubMedPubMedCentralCrossRef
145.
go back to reference Deneault E, Faheem M, White SH, Rodrigues DC, Sun S, Wei W, et al. CNTN5(-)(/+)or EHMT2(-)(/+)human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks. Elife. 2019;8. Deneault E, Faheem M, White SH, Rodrigues DC, Sun S, Wei W, et al. CNTN5(-)(/+)or EHMT2(-)(/+)human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks. Elife. 2019;8.
146.
go back to reference Zaslavsky K, Zhang WB, McCready FP, Rodrigues DC, Deneault E, Loo C, et al. SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons. Nat Neurosci. 2019;22(4):556–64.PubMedPubMedCentralCrossRef Zaslavsky K, Zhang WB, McCready FP, Rodrigues DC, Deneault E, Loo C, et al. SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons. Nat Neurosci. 2019;22(4):556–64.PubMedPubMedCentralCrossRef
147.
go back to reference Deneault E, White SH, Rodrigues DC, Ross PJ, Faheem M, Zaslavsky K, et al. Complete disruption of autism-susceptibility genes by gene editing predominantly reduces functional connectivity of isogenic human neurons. Stem Cell Rep. 2018;11(5):1211–25.CrossRef Deneault E, White SH, Rodrigues DC, Ross PJ, Faheem M, Zaslavsky K, et al. Complete disruption of autism-susceptibility genes by gene editing predominantly reduces functional connectivity of isogenic human neurons. Stem Cell Rep. 2018;11(5):1211–25.CrossRef
148.
go back to reference Abu Diab M, Eiges R. The contribution of pluripotent stem cell (PSC)-based models to the study of fragile X syndrome (FXS). Brain Sci. 2019;9(2). Abu Diab M, Eiges R. The contribution of pluripotent stem cell (PSC)-based models to the study of fragile X syndrome (FXS). Brain Sci. 2019;9(2).
149.
go back to reference Vershkov D, Ben-Hur T, Benvenisty N. Chapter 6 - Modeling fragile X syndrome using human pluripotent stem cells. In: Willemsen R, Kooy RF, editors. Fragile X Syndrome: Academic Press; 2017. p. 103–21. Vershkov D, Ben-Hur T, Benvenisty N. Chapter 6 - Modeling fragile X syndrome using human pluripotent stem cells. In: Willemsen R, Kooy RF, editors. Fragile X Syndrome: Academic Press; 2017. p. 103–21.
150.
151.
go back to reference Lee KM, Hawi ZH, Parkington HC, Parish CL, Kumar PV, Polo JM, et al. The application of human pluripotent stem cells to model the neuronal and glial components of neurodevelopmental disorders. Mol Psychiatry. 2020;25(2):368–78.PubMedCrossRef Lee KM, Hawi ZH, Parkington HC, Parish CL, Kumar PV, Polo JM, et al. The application of human pluripotent stem cells to model the neuronal and glial components of neurodevelopmental disorders. Mol Psychiatry. 2020;25(2):368–78.PubMedCrossRef
152.
go back to reference Shen X, Yeung HT, Lai KO. Application of human-induced pluripotent stem cells (hiPSCs) to study synaptopathy of neurodevelopmental disorders. Dev Neurobiol. 2019;79(1):20–35.PubMedCrossRef Shen X, Yeung HT, Lai KO. Application of human-induced pluripotent stem cells (hiPSCs) to study synaptopathy of neurodevelopmental disorders. Dev Neurobiol. 2019;79(1):20–35.PubMedCrossRef
153.
go back to reference Ben-Reuven L, Reiner O. Modeling the autistic cell: iPSCs recapitulate developmental principles of syndromic and nonsyndromic ASD. Dev Growth Different. 2016;58(5):481–91.CrossRef Ben-Reuven L, Reiner O. Modeling the autistic cell: iPSCs recapitulate developmental principles of syndromic and nonsyndromic ASD. Dev Growth Different. 2016;58(5):481–91.CrossRef
154.
go back to reference Blair JD, Bateup HS. New frontiers in modeling tuberous sclerosis with human stem cell-derived neurons and brain organoids. Dev Dyn. 2020;249(1):46–55.PubMedCrossRef Blair JD, Bateup HS. New frontiers in modeling tuberous sclerosis with human stem cell-derived neurons and brain organoids. Dev Dyn. 2020;249(1):46–55.PubMedCrossRef
155.
go back to reference Pramparo T, Lombardo MV, Campbell K, Barnes CC, Marinero S, Solso S, et al. Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers. Mol Syst Biol. 2015;11(12). Pramparo T, Lombardo MV, Campbell K, Barnes CC, Marinero S, Solso S, et al. Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers. Mol Syst Biol. 2015;11(12).
156.
go back to reference Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45.PubMedCrossRef Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45.PubMedCrossRef
157.
go back to reference Sacco R, Gabriele S, Persico AM. Head circumference and brain size in autism spectrum disorder: a systematic review and meta-analysis. Psychiatry Res. 2015;234(2):239–51.PubMedCrossRef Sacco R, Gabriele S, Persico AM. Head circumference and brain size in autism spectrum disorder: a systematic review and meta-analysis. Psychiatry Res. 2015;234(2):239–51.PubMedCrossRef
158.
go back to reference Dong D, Zielke HR, Yeh D, Yang P. Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder. Autism Res. 2018;11(7):1076–90.PubMedPubMedCentralCrossRef Dong D, Zielke HR, Yeh D, Yang P. Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder. Autism Res. 2018;11(7):1076–90.PubMedPubMedCentralCrossRef
159.
go back to reference van Rooij D, Anagnostou E, Arango C, Auzias G, Behrmann M, Busatto GF, et al. Cortical and subcortical brain morphometry differences between patients with autism spectrum disorder and healthy individuals across the lifespan: results from the ENIGMA ASD Working Group. AJP. 2017;175(4):359–69.CrossRef van Rooij D, Anagnostou E, Arango C, Auzias G, Behrmann M, Busatto GF, et al. Cortical and subcortical brain morphometry differences between patients with autism spectrum disorder and healthy individuals across the lifespan: results from the ENIGMA ASD Working Group. AJP. 2017;175(4):359–69.CrossRef
160.
go back to reference Button KS, Ioannidis JPA, Mokrysz C, Nosek BA, Flint J, Robinson ESJ, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14(5):365–76.PubMedCrossRef Button KS, Ioannidis JPA, Mokrysz C, Nosek BA, Flint J, Robinson ESJ, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14(5):365–76.PubMedCrossRef
161.
go back to reference Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature. 2016. Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature. 2016.
162.
go back to reference Velmeshev D, Schirmer L, Jung D, Haeussler M, Perez Y, Mayer S, et al. Single-cell genomics identifies cell type–specific molecular changes in autism. Science. 2019;364(6441):685–9.PubMedCrossRefPubMedCentral Velmeshev D, Schirmer L, Jung D, Haeussler M, Perez Y, Mayer S, et al. Single-cell genomics identifies cell type–specific molecular changes in autism. Science. 2019;364(6441):685–9.PubMedCrossRefPubMedCentral
163.
go back to reference Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011;474(7351):380–4.PubMedPubMedCentralCrossRef Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011;474(7351):380–4.PubMedPubMedCentralCrossRef
164.
go back to reference Abraham JR, Szoko N, Barnard J, Rubin RA, Schlatzer D, Lundberg K, et al. Proteomic investigations of autism brain identify known and novel pathogenetic processes. Sci Rep. 2019;9(1):13118.PubMedPubMedCentralCrossRef Abraham JR, Szoko N, Barnard J, Rubin RA, Schlatzer D, Lundberg K, et al. Proteomic investigations of autism brain identify known and novel pathogenetic processes. Sci Rep. 2019;9(1):13118.PubMedPubMedCentralCrossRef
165.
go back to reference Gandal MJ, Haney JR, Parikshak NN, Leppa V, Ramaswami G, Hartl C, et al. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science. 2018;359(6376):693–7.PubMedPubMedCentralCrossRef Gandal MJ, Haney JR, Parikshak NN, Leppa V, Ramaswami G, Hartl C, et al. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science. 2018;359(6376):693–7.PubMedPubMedCentralCrossRef
166.
go back to reference Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362(6420). Gandal MJ, Zhang P, Hadjimichael E, Walker RL, Chen C, Liu S, et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science. 2018;362(6420).
167.
go back to reference Liu X, Campanac E, Cheung HH, Ziats MN, Canterel-Thouennon L, Raygada M, et al. Idiopathic autism: cellular and molecular phenotypes in pluripotent stem cell-derived neurons. Mol Neurobiol. 2016. Liu X, Campanac E, Cheung HH, Ziats MN, Canterel-Thouennon L, Raygada M, et al. Idiopathic autism: cellular and molecular phenotypes in pluripotent stem cell-derived neurons. Mol Neurobiol. 2016.
168.
go back to reference Sohal VS, Rubenstein JLR. Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders. Mol Psychiatry. 2019;24(9):1248–57.PubMedPubMedCentralCrossRef Sohal VS, Rubenstein JLR. Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders. Mol Psychiatry. 2019;24(9):1248–57.PubMedPubMedCentralCrossRef
169.
go back to reference Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, et al. Self-organized cerebral organoids with human-specific features predict effective drugs to combat Zika virus infection. Cell Rep. 2017;21(2):517–32.PubMedPubMedCentralCrossRef Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, et al. Self-organized cerebral organoids with human-specific features predict effective drugs to combat Zika virus infection. Cell Rep. 2017;21(2):517–32.PubMedPubMedCentralCrossRef
170.
go back to reference Du F, Yu Q, Chen A, Chen D, Yan SS. Astrocytes attenuate mitochondrial dysfunctions in human dopaminergic neurons derived from iPSC. Stem Cell Rep. 2018;10(2):366–74.CrossRef Du F, Yu Q, Chen A, Chen D, Yan SS. Astrocytes attenuate mitochondrial dysfunctions in human dopaminergic neurons derived from iPSC. Stem Cell Rep. 2018;10(2):366–74.CrossRef
171.
go back to reference Tripathi P, Rodriguez-Muela N, Klim JR, de Boer AS, Agrawal S, Sandoe J, et al. Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-β1. Stem Cell Rep. 2017;9(2):667–80.CrossRef Tripathi P, Rodriguez-Muela N, Klim JR, de Boer AS, Agrawal S, Sandoe J, et al. Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-β1. Stem Cell Rep. 2017;9(2):667–80.CrossRef
172.
go back to reference Donovan APA, Basson MA. The neuroanatomy of autism – a developmental perspective. J Anatomy. 2017;230(1):4–15.CrossRef Donovan APA, Basson MA. The neuroanatomy of autism – a developmental perspective. J Anatomy. 2017;230(1):4–15.CrossRef
173.
go back to reference Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 2015;10(4):537–50.PubMedCrossRef Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 2015;10(4):537–50.PubMedCrossRef
174.
go back to reference Jo J, Xiao Y, Sun Alfred X, Cukuroglu E, Tran H-D, Göke J, et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell. 2016;19(2):248–57.PubMedPubMedCentralCrossRef Jo J, Xiao Y, Sun Alfred X, Cukuroglu E, Tran H-D, Göke J, et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell. 2016;19(2):248–57.PubMedPubMedCentralCrossRef
175.
go back to reference Nicholas CR, Chen J, Tang Y, Southwell DG, Chalmers N, Vogt D, et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell. 2013;12(5):573–86.PubMedPubMedCentralCrossRef Nicholas CR, Chen J, Tang Y, Southwell DG, Chalmers N, Vogt D, et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell. 2013;12(5):573–86.PubMedPubMedCentralCrossRef
176.
go back to reference Merkle FT, Maroof A, Wataya T, Sasai Y, Studer L, Eggan K, et al. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development. 2015;142(4):633–43.PubMedPubMedCentralCrossRef Merkle FT, Maroof A, Wataya T, Sasai Y, Studer L, Eggan K, et al. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development. 2015;142(4):633–43.PubMedPubMedCentralCrossRef
177.
go back to reference Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, et al. Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output. Nat Neurosci. 2019;22(4):669.PubMedPubMedCentralCrossRef Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, et al. Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output. Nat Neurosci. 2019;22(4):669.PubMedPubMedCentralCrossRef
178.
go back to reference Stogsdill JA, Eroglu C. The interplay between neurons and glia in synapse development and plasticity. Curr Opin Neurobiol. 2017;42:1–8.PubMedCrossRef Stogsdill JA, Eroglu C. The interplay between neurons and glia in synapse development and plasticity. Curr Opin Neurobiol. 2017;42:1–8.PubMedCrossRef
179.
go back to reference Reemst K, Noctor SC, Lucassen PJ, Hol EM. The indispensable roles of microglia and astrocytes during brain development. Front Hum Neurosci. 2016;10. Reemst K, Noctor SC, Lucassen PJ, Hol EM. The indispensable roles of microglia and astrocytes during brain development. Front Hum Neurosci. 2016;10.
180.
go back to reference Germain PL, Testa G. Taming Human genetic variability: transcriptomic meta-analysis guides the experimental design and interpretation of iPSC-based disease modeling. Stem Cell Rep. 2017;8(6):1784–96.CrossRef Germain PL, Testa G. Taming Human genetic variability: transcriptomic meta-analysis guides the experimental design and interpretation of iPSC-based disease modeling. Stem Cell Rep. 2017;8(6):1784–96.CrossRef
181.
go back to reference Lomax GP, DeWitt ND, Millan MT, Feigal EG. How California Institute for Regenerative Medicine research programs support science and regulatory policy. Stem Cells Transl Med. 2014;3(6):673–4.PubMedPubMedCentralCrossRef Lomax GP, DeWitt ND, Millan MT, Feigal EG. How California Institute for Regenerative Medicine research programs support science and regulatory policy. Stem Cells Transl Med. 2014;3(6):673–4.PubMedPubMedCentralCrossRef
182.
go back to reference De Sousa PA, Steeg R, Wachter E, Bruce K, King J, Hoeve M, et al. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience. Stem Cell Res. 2017;20:105–14.PubMedCrossRef De Sousa PA, Steeg R, Wachter E, Bruce K, King J, Hoeve M, et al. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience. Stem Cell Res. 2017;20:105–14.PubMedCrossRef
183.
go back to reference Kim J-H, Kurtz A, Yuan B-Z, Zeng F, Lomax G, Loring JF, et al. Report of the International Stem Cell Banking Initiative Workshop Activity: current hurdles and progress in seed-stock banking of human pluripotent stem cells. Stem Cells Transl Med. 2017;6(11):1956–62.PubMedPubMedCentralCrossRef Kim J-H, Kurtz A, Yuan B-Z, Zeng F, Lomax G, Loring JF, et al. Report of the International Stem Cell Banking Initiative Workshop Activity: current hurdles and progress in seed-stock banking of human pluripotent stem cells. Stem Cells Transl Med. 2017;6(11):1956–62.PubMedPubMedCentralCrossRef
184.
go back to reference Sridharan B, Hubbs C, Llamosas N, Kilinc M, Singhera FU, Willems E, et al. A simple procedure for creating scalable phenotypic screening assays in human neurons. Sci Rep. 2019;9(1):9000.PubMedPubMedCentralCrossRef Sridharan B, Hubbs C, Llamosas N, Kilinc M, Singhera FU, Willems E, et al. A simple procedure for creating scalable phenotypic screening assays in human neurons. Sci Rep. 2019;9(1):9000.PubMedPubMedCentralCrossRef
185.
go back to reference Marton RM, Miura Y, Sloan SA, Li Q, Revah O, Levy RJ, et al. Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures. Nat Neurosci. 2019. Marton RM, Miura Y, Sloan SA, Li Q, Revah O, Levy RJ, et al. Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures. Nat Neurosci. 2019.
186.
go back to reference Madhavan M, Nevin ZS, Shick HE, Garrison E, Clarkson-Paredes C, Karl M, et al. Induction of myelinating oligodendrocytes in human cortical spheroids. Nat Methods. 2018;15(9):700–6.PubMedPubMedCentralCrossRef Madhavan M, Nevin ZS, Shick HE, Garrison E, Clarkson-Paredes C, Karl M, et al. Induction of myelinating oligodendrocytes in human cortical spheroids. Nat Methods. 2018;15(9):700–6.PubMedPubMedCentralCrossRef
187.
go back to reference McQuade A, Coburn M, Tu CH, Hasselmann J, Davtyan H, Blurton-Jones M. Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol Neurodegener. 2018;13(1):67.PubMedPubMedCentralCrossRef McQuade A, Coburn M, Tu CH, Hasselmann J, Davtyan H, Blurton-Jones M. Development and validation of a simplified method to generate human microglia from pluripotent stem cells. Mol Neurodegener. 2018;13(1):67.PubMedPubMedCentralCrossRef
188.
go back to reference Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, et al. iPSC-derived human microglia-like cells to study neurological diseases. Neuron. 2017;94(2):278–93 e9.PubMedPubMedCentralCrossRef Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, et al. iPSC-derived human microglia-like cells to study neurological diseases. Neuron. 2017;94(2):278–93 e9.PubMedPubMedCentralCrossRef
189.
go back to reference Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, et al. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med. 2016;22(11):1358–67.PubMedPubMedCentralCrossRef Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, et al. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med. 2016;22(11):1358–67.PubMedPubMedCentralCrossRef
190.
go back to reference Oksdath M, Perrin SL, Bardy C, Hilder EF, DeForest CA, Arrua RD, et al. Review: Synthetic scaffolds to control the biochemical, mechanical, and geometrical environment of stem cell-derived brain organoids. APL Bioeng. 2018;2(4):041501.PubMedPubMedCentralCrossRef Oksdath M, Perrin SL, Bardy C, Hilder EF, DeForest CA, Arrua RD, et al. Review: Synthetic scaffolds to control the biochemical, mechanical, and geometrical environment of stem cell-derived brain organoids. APL Bioeng. 2018;2(4):041501.PubMedPubMedCentralCrossRef
192.
go back to reference Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19(5):646–51.PubMedPubMedCentralCrossRef Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19(5):646–51.PubMedPubMedCentralCrossRef
193.
go back to reference Qi Y, Zhang X-J, Renier N, Wu Z, Atkin T, Sun Z, et al. Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat Biotechnol. 2017;35(2):154–63.PubMedPubMedCentralCrossRef Qi Y, Zhang X-J, Renier N, Wu Z, Atkin T, Sun Z, et al. Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat Biotechnol. 2017;35(2):154–63.PubMedPubMedCentralCrossRef
194.
go back to reference Canfield SG, Stebbins MJ, Faubion MG, Gastfriend BD, Palecek SP, Shusta EV. An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons. Fluids Barriers CNS. 2019;16(1):25.PubMedPubMedCentralCrossRef Canfield SG, Stebbins MJ, Faubion MG, Gastfriend BD, Palecek SP, Shusta EV. An isogenic neurovascular unit model comprised of human induced pluripotent stem cell-derived brain microvascular endothelial cells, pericytes, astrocytes, and neurons. Fluids Barriers CNS. 2019;16(1):25.PubMedPubMedCentralCrossRef
195.
go back to reference Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, et al. An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol. 2018;36(5):432–41.PubMedPubMedCentralCrossRef Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, et al. An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol. 2018;36(5):432–41.PubMedPubMedCentralCrossRef
196.
go back to reference Daviaud N, Friedel RH, Zou H. Vascularization and Engraftment of transplanted human cerebral organoids in mouse cortex. eNeuro. 2018;5(6). Daviaud N, Friedel RH, Zou H. Vascularization and Engraftment of transplanted human cerebral organoids in mouse cortex. eNeuro. 2018;5(6).
Metadata
Title
Human in vitro models for understanding mechanisms of autism spectrum disorder
Authors
Aaron Gordon
Daniel H. Geschwind
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2020
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-020-00332-7

Other articles of this Issue 1/2020

Molecular Autism 1/2020 Go to the issue