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Journal Article

Expression of Lineage Transcription Factors Identifies Differences in Transition States of Induced Human Oligodendrocyte Differentiation

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Raabe,  Florian J.
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Stephan,  Marius
IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Ziller,  Michael J.
RG Genomics of Complex Diseases, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Raabe, F. J., Stephan, M., Waldeck, J. B., Huber, V., Demetriou, D., Kannaiyan, N., et al. (2022). Expression of Lineage Transcription Factors Identifies Differences in Transition States of Induced Human Oligodendrocyte Differentiation. CELLS, 11(2): 241. doi:10.3390/cells11020241.


Cite as: https://hdl.handle.net/21.11116/0000-000A-3BE6-1
Abstract
Oligodendrocytes (OLs) are critical for myelination and are implicated in several brain disorders. Directed differentiation of human-induced OLs (iOLs) from pluripotent stem cells can be achieved by forced expression of different combinations of the transcription factors SOX10 (S), OLIG2 (O), and NKX6.2 (N). Here, we applied quantitative image analysis and single-cell transcriptomics to compare different transcription factor (TF) combinations for their efficacy towards robust OL lineage conversion. Compared with S alone, the combination of SON increases the number of iOLs and generates iOLs with a more complex morphology and higher expression levels of myelin-marker genes. RNA velocity analysis of individual cells reveals that S generates a population of oligodendrocyte-precursor cells (OPCs) that appear to be more immature than those generated by SON and to display distinct molecular properties. Our work highlights that TFs for generating iOPCs or iOLs should be chosen depending on the intended application or research question, and that SON might be beneficial to study more mature iOLs while S might be better suited to investigate iOPC biology.