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Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Epilepsy | Review

The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery

Authors: Wireko Andrew Awuah, Arjun Ahluwalia, Shankaneel Ghosh, Sakshi Roy, Joecelyn Kirani Tan, Favour Tope Adebusoye, Tomas Ferreira, Hareesha Rishab Bharadwaj, Vallabh Shet, Mrinmoy Kundu, Amanda Leong Weng Yee, Toufik Abdul-Rahman, Oday Atallah

Published in: European Journal of Medical Research | Issue 1/2023

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Abstract

Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.
Literature
8.
11.
17.
go back to reference Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Aghi MK. Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. J Clin Investig. 2023;133(5): e147087. https://doi.org/10.1172/JCI147087.CrossRefPubMedPubMedCentral Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Aghi MK. Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. J Clin Investig. 2023;133(5): e147087. https://​doi.​org/​10.​1172/​JCI147087.CrossRefPubMedPubMedCentral
19.
23.
go back to reference Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Wang E, Horgusluoglu-Moloch E, Song WM, Li A, Castranio EL, Tcw J, Ho L, Goate A, Fossati V, Noggle S, Gandy S, Ehrlich ME, Katsel P, Schadt E, Zhang B. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Sci Adv. 2021;7(2): eabb5398. https://doi.org/10.1126/sciadv.abb5398.CrossRefPubMedPubMedCentral Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Wang E, Horgusluoglu-Moloch E, Song WM, Li A, Castranio EL, Tcw J, Ho L, Goate A, Fossati V, Noggle S, Gandy S, Ehrlich ME, Katsel P, Schadt E, Zhang B. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Sci Adv. 2021;7(2): eabb5398. https://​doi.​org/​10.​1126/​sciadv.​abb5398.CrossRefPubMedPubMedCentral
26.
go back to reference Smajić S, Prada-Medina CA, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C, Jarazo J, Henck J, Balachandran S, Pachchek S, Morris CM, Antony P, Timmermann B, Sauer S, Pereira SL, Schwamborn JC, May P, Grünewald A, Spielmann M. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain. 2022;145(3):964–78. https://doi.org/10.1093/brain/awab446.CrossRefPubMed Smajić S, Prada-Medina CA, Landoulsi Z, Ghelfi J, Delcambre S, Dietrich C, Jarazo J, Henck J, Balachandran S, Pachchek S, Morris CM, Antony P, Timmermann B, Sauer S, Pereira SL, Schwamborn JC, May P, Grünewald A, Spielmann M. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain. 2022;145(3):964–78. https://​doi.​org/​10.​1093/​brain/​awab446.CrossRefPubMed
31.
go back to reference Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, Pflueger J, Lister R, Rackham OJL, Petretto E, Polo JM. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat Neurosci. 2019;22(12):2087–97. https://doi.org/10.1038/s41593-019-0539-4.CrossRefPubMed Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, Pflueger J, Lister R, Rackham OJL, Petretto E, Polo JM. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat Neurosci. 2019;22(12):2087–97. https://​doi.​org/​10.​1038/​s41593-019-0539-4.CrossRefPubMed
37.
38.
go back to reference Curry RN, Aiba I, Meyer J, Lozzi B, Ko Y, McDonald MF, Rosenbaum A, Cervantes A, Huang-Hobbs E, Cocito C, Greenfield JP, Jalali A, Gavvala J, Mohila C, Serin Harmanci A, Noebels J, Rao G, Deneen B. Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation. Neuron. 2023;111(5):682-695.e9. https://doi.org/10.1016/j.neuron.2023.01.013.CrossRefPubMed Curry RN, Aiba I, Meyer J, Lozzi B, Ko Y, McDonald MF, Rosenbaum A, Cervantes A, Huang-Hobbs E, Cocito C, Greenfield JP, Jalali A, Gavvala J, Mohila C, Serin Harmanci A, Noebels J, Rao G, Deneen B. Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation. Neuron. 2023;111(5):682-695.e9. https://​doi.​org/​10.​1016/​j.​neuron.​2023.​01.​013.CrossRefPubMed
39.
49.
54.
go back to reference Gojo J, Englinger B, Jiang L, Hübner JM, Shaw ML, Hack OA, Madlener S, Kirchhofer D, Liu I, Pyrdol J, Hovestadt V, Mazzola E, Mathewson ND, Trissal M, Lötsch D, Dorfer C, Haberler C, Halfmann A, Mayr L, Filbin MG. Single-cell RNA-seq reveals cellular hierarchies and impaired developmental trajectories in pediatric ependymoma. Cancer Cell. 2020;38(1):44-59.e9. https://doi.org/10.1016/j.ccell.2020.06.004.CrossRefPubMedCentral Gojo J, Englinger B, Jiang L, Hübner JM, Shaw ML, Hack OA, Madlener S, Kirchhofer D, Liu I, Pyrdol J, Hovestadt V, Mazzola E, Mathewson ND, Trissal M, Lötsch D, Dorfer C, Haberler C, Halfmann A, Mayr L, Filbin MG. Single-cell RNA-seq reveals cellular hierarchies and impaired developmental trajectories in pediatric ependymoma. Cancer Cell. 2020;38(1):44-59.e9. https://​doi.​org/​10.​1016/​j.​ccell.​2020.​06.​004.CrossRefPubMedCentral
87.
go back to reference Menon S, Lui VC, Tam PK. Bioinformatics tools and methods to analyze single-cell RNA sequencing data. Bioinformatics. 2021;6(8). Menon S, Lui VC, Tam PK. Bioinformatics tools and methods to analyze single-cell RNA sequencing data. Bioinformatics. 2021;6(8).
105.
go back to reference Garofano L, Migliozzi S, Oh YT, D’Angelo F, Najac RD, Ko A, Frangaj B, Caruso FP, Yu K, Yuan J, Zhao W, Di Stefano AL, Bielle F, Jiang T, Sims P, Suvà ML, Tang F, Su XD, Ceccarelli M, Sanson M, et al. Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Nat Cancer. 2021;2(2):141–56. https://doi.org/10.1038/s43018-020-00159-4.CrossRefPubMedPubMedCentral Garofano L, Migliozzi S, Oh YT, D’Angelo F, Najac RD, Ko A, Frangaj B, Caruso FP, Yu K, Yuan J, Zhao W, Di Stefano AL, Bielle F, Jiang T, Sims P, Suvà ML, Tang F, Su XD, Ceccarelli M, Sanson M, et al. Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Nat Cancer. 2021;2(2):141–56. https://​doi.​org/​10.​1038/​s43018-020-00159-4.CrossRefPubMedPubMedCentral
Metadata
Title
The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery
Authors
Wireko Andrew Awuah
Arjun Ahluwalia
Shankaneel Ghosh
Sakshi Roy
Joecelyn Kirani Tan
Favour Tope Adebusoye
Tomas Ferreira
Hareesha Rishab Bharadwaj
Vallabh Shet
Mrinmoy Kundu
Amanda Leong Weng Yee
Toufik Abdul-Rahman
Oday Atallah
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01504-w

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