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Current Oncology Reports

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01-05-2018 | Neuro-oncology (S Nagpal, Section Editor)

Single-Cell RNA-Sequencing in Glioma

Authors: Eli Johnson, Katherine L. Dickerson, Ian D. Connolly, Melanie Hayden Gephart

Published in: Current Oncology Reports | Issue 5/2018

Abstract

Purpose of Review

In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas.

Recent Findings

Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process.

Summary

Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.

Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009;10:57–63.CrossRefPubMedPubMedCentral

Berger MF, Levin JZ, Vijayendran K, Sivachenko A, Adiconis X, Maguire J, et al. Integrative analysis of the melanoma transcriptome. Genome Res. 2010;20(4):413–27. https://doi.org/10.1101/gr.103697.109.CrossRefPubMedPubMedCentral

Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010;28(5):511–5. https://doi.org/10.1038/nbt.1621.CrossRefPubMedPubMedCentral

• Tirosh I, Venteicher AS, Hebert C, et al. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016;539:309–13. This paper provides evidence that a subpopulation of proliferating stem-like cells may drive growth of IDH-A and IDH-O gliomas. CrossRefPubMedPubMedCentral

Griffith M, Griffith OL, Mwenifumbo J, Goya R, Morrissy AS, Morin RD, et al. Alternative expression analysis by RNA sequencing. Nat Methods. 2010;7(10):843–7. https://doi.org/10.1038/nmeth.1503.CrossRefPubMed

Wang L, Xi Y, Yu J, Dong L, Yen L, Li W. A statistical method for the detection of alternative splicing using RNA-seq. PLoS One. 2010;5(1):e8529. https://doi.org/10.1371/journal.pone.0008529.CrossRefPubMedPubMedCentral

Hedlund E, Deng Q. Single-cell RNA sequencing: technical advancements and biological applications. Mol Asp Med. 2017;59:36–46. https://doi.org/10.1016/j.mam.2017.07.003.CrossRef

Louis DN, Perry A, Burger P, et al. International society of neuropathology—Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol. 2014;24:429–35.CrossRefPubMed

Mack SC, Northcott PA. Genomic analysis of childhood brain tumors: methods for genome-wide discovery and precision medicine become mainstream. J Clin Oncol. 2017;35(21):2346–54. https://doi.org/10.1200/JCO.2017.72.9921.CrossRefPubMed

10.

Nikiforova MN, Wald AI, Melan MA, Roy S, Zhong S, Hamilton RL, et al. Targeted next-generation sequencing panel (GlioSeq) provides comprehensive genetic profiling of central nervous system tumors. Neuro-Oncology. 2016;18(3):379–87. https://doi.org/10.1093/neuonc/nov289.CrossRefPubMed

11.

Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002;415:436–42.CrossRefPubMed

12.

Tirosh I, Suva ML. Dissecting human gliomas by single-cell RNA sequencing. Neuro-Oncology. 2017;20(1):37–43. https://doi.org/10.1093/neuonc/nox126.CrossRef

13.

Huse JT, Aldape KD. The evolving role of molecular markers in the diagnosis and management of diffuse glioma. Clin Cancer Res. 2014;20(22):5601–11. https://doi.org/10.1158/1078-0432.CCR-14-0831.CrossRefPubMed

14.

Zeisel A, Munoz-Manchado AB, Codeluppi S, et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015;347(6226):1138–42. https://doi.org/10.1126/science.aaa1934.CrossRefPubMed

15.

Buenrostro JD, Wu B, Litzenburger UM, Ruff D, Gonzales ML, Snyder MP, et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature. 2015;523(7561):486–90. https://doi.org/10.1038/nature14590.CrossRefPubMedPubMedCentral

16.

Treutlein B, Brownfield DG, Wu AR, Neff NF, Mantalas GL, Espinoza FH, et al. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature. 2014;509(7500):371–5. https://doi.org/10.1038/nature13173.CrossRefPubMedPubMedCentral

17.

Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol. 2014;32(5):479–84. https://doi.org/10.1038/nbt.2892.CrossRefPubMedPubMedCentral

18.

Hashimshony T, Wagner F, Sher N, Yanai I. CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep. 2012;2(3):666–73. https://doi.org/10.1016/j.celrep.2012.08.003.CrossRefPubMed

19.

Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H, Peat J, et al. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods. 2014;11(8):817–20. https://doi.org/10.1038/nmeth.3035.CrossRefPubMedPubMedCentral

20.

Shalek AK, Satija R, Adiconis X, et al. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature. 2013;498:236–40.CrossRefPubMedPubMedCentral

21.

Shalek AK, Satija R, Shuga J, et al. Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature. 2014;510:363–9.CrossRefPubMedPubMedCentral

22.

Tirosh I, Izar B, Prakadan SM, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016;352:189–96.CrossRefPubMedPubMedCentral

23.

Gierahn TM, Wadsworth MH 2nd, Hughes TK, Bryson BD, Butler A, Satija R, et al. Seq-well: portable, low-cost RNA sequencing of single cells at high throughput. Nat Methods. 2017;14(4):395–8. https://doi.org/10.1038/nmeth.4179.CrossRefPubMedPubMedCentral

24.

Shin J, Berg DA, Zhu Y, Shin JY, Song J, Bonaguidi MA, et al. Single-cell RNA-Seq with waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell. 2015;17(3):360–72. https://doi.org/10.1016/j.stem.2015.07.013.CrossRefPubMed

25.

Llorens-Bobadilla E, Zhao S, Baser A, Saiz-Castro G, Zwadlo K, Martin-Villalba A. Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell. 2015;17(3):329–40. https://doi.org/10.1016/j.stem.2015.07.002.CrossRefPubMed

26.

Gokce O, Stanley GM, Treutlein B, Neff NF, Camp JG, Malenka RC, et al. Cellular taxonomy of the mouse striatum as revealed by single-cell RNA-Seq. Cell Rep. 2016;16(4):1126–37. https://doi.org/10.1016/j.celrep.2016.06.059.CrossRefPubMedPubMedCentral

27.

Tasic B, Menon V, Nguyen TN, et al. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat Neurosci. 2016;19:335–46.CrossRefPubMedPubMedCentral

28.

• Darmanis S, Sloan SA, Zhang Y, Enge M, Caneda C, Shuer LM, Hayden Gephart MG, Barres BA, Quake SR. A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci USA. 2015;112:7285–90. https://doi.org/10.1073/pnas.1507125112. This paper successfully showed the efficacy of scRNA-seq in normal adult and fetal brain.

29.

Cuevas-Diaz Duran R, Wei H, Wu JQ. Single-cell RNA-sequencing of the brain. Clin Transl Med. 2017;6(1):20. https://doi.org/10.1186/s40169-017-0150-9.CrossRefPubMedPubMedCentral

30.

Patel AP, Tirosh I, Trombetta JJ, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396–140124.CrossRefPubMedPubMedCentral

31.

Müller S, Liu SJ, Di Lullo E, et al. Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas. Mol Syst Biol. 2016;12:889. https://doi.org/10.15252/msb.20166969.

32.

• Wang Q, Hu B, Hu X, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32:42–56.e6. This paper examines the immunologic effects of the TME on GBM by subtype. CrossRefPubMed

33.

•• Darmanis S, Sloan SA, Croote D, et al. Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep. 2017;21:1399–410. This paper provides the most comprehensive analysis of GBM at the single-cell level. CrossRefPubMedPubMedCentral

34.

•• Venteicher AS, Tirosh I, Hebert C, et al. Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science. 2017; https://doi.org/10.1126/science.aai8478. This paper reports a strong influence of the TME, and common developmental lineages in IDH-A and IDH-O gliomas using a large sample size.

35.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20. https://doi.org/10.1007/s00401-016-1545-1.CrossRefPubMed

36.

Cheng Y-K, Beroukhim R, Levine RL, Mellinghoff IK, Holland EC, Michor F. A mathematical methodology for determining the temporal order of pathway alterations arising during gliomagenesis. PLoS Comput Biol. 2012;8(1):e1002337. https://doi.org/10.1371/journal.pcbi.1002337.CrossRefPubMedPubMedCentral

37.

Brat DJ, Verhaak RGW, Aldape KD, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481–98. https://doi.org/10.1056/NEJMoa1402121.CrossRefPubMed

38.

Verhaak RGW, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98–110. https://doi.org/10.1016/j.ccr.2009.12.020.CrossRefPubMedPubMedCentral

39.

Filbin MG, Suvà ML. Gliomas genomics and epigenomics: arriving at the start and knowing it for the first time. Annu Rev Pathol Mech Dis. 2016;11(1):497–521. https://doi.org/10.1146/annurev-pathol-012615-044208.CrossRef

40.

Brennan CW, Verhaak RGW, McKenna A, Campos B, Noushmehr H, Salama SR, et al. The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–77. https://doi.org/10.1016/j.cell.2013.09.034.CrossRefPubMedPubMedCentral

41.

Chen J, Li Y, Yu T-S, McKay RM, Burns DK, Kernie SG, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature. 2012;488(7412):522–6. https://doi.org/10.1038/nature11287.CrossRefPubMedPubMedCentral

Title: Single-Cell RNA-Sequencing in Glioma
Authors: Eli Johnson
Katherine L. Dickerson
Ian D. Connolly
Melanie Hayden Gephart
Publication date: 01-05-2018
Publisher: Springer US
Published in: Current Oncology Reports / Issue 5/2018
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI: https://doi.org/10.1007/s11912-018-0673-2

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Abstract

Purpose of Review

Recent Findings

Summary

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