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Single-Cell Transcriptomic Analysis Reveals Molecular Diversity of Human Oligodendrocyte Progenitor Cells

ABSTRACT: We performed single-cell-transcriptomic-analysis of developing human stem cell-derived oligodendrocyte-precursor-cells (hOPCs). We studied both a genome engineered hESC-reporter lines, containing an Identification-and-Purification tag expressed under control of the endogenous, OPC-specific, PDGFRa promoter, and an unmodified iPSC line, and performed time-course single-cell-RNA-sequencing of purified hOPCs. Our analysis uncovered transcriptional heterogeneity of PDGFRa+ hOPCs and identified regulatory genes and networks that control their differentiation and myelination competence. Pseudotime trajectory analysis suggested distinct trajectories for the development of oligodendrocytes vs astrocytes from the hOPCs. We also identified novel transcription factors and other genes that developing hOPCs potentially use to choose between oligodendrocyte vs astrocyte lineages. In addition, pathway enrichment analysis followed by pharmacological intervention of those pathways confirm that mTOR and cholesterol biosynthesis signaling pathways are involved in maturation of oligodendrocytes from hOPCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146373 | GEO | 2020/03/05

REPOSITORIES: GEO

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