Transcription factor induction of human oligodendrocyte progenitor fate and differentiation
Open accessAbstract
Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a(+)O4(+) OPCs relative to CD133(+)CD140a(-) neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs.
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The proximal 1.5 kb human MAG promoter fragment lacks YY1 and Id4 motifs but contains binding sites for Olig1 and Sox10 and an evolutionarily highly conserved sequence.
“We therefore decided to also investigate the proximal 1.5 kb of the long fragment since this fragment was devoid of these motifs but contained binding sites for myelin cell lineage factors Oligodendrocyte Transcription Factor 1 (Olig1) and SRY-Box 10 (Sox10) and an evolutionary highly conserved sequence (Wang et al., 2014).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Wang et al., 2014
The Results discuss a conserved SOX10 enhancer, not the human MAG promoter. Searches for the 1.5 kb MAG promoter fragment, YY1 and Id4 motifs, and Olig1/Sox10 binding sites found no passage addressing the claimed promoter features. (LLM, conf=0.76)
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“…investigate the proximal 1.5 kb of the long fragment since this fragment was devoid of these motifs but contained binding sites for myelin cell lineage factors Oligodendrocyte Transcription Factor 1 (Olig1) and SRYBox 10 (Sox10) and an evolutionary highly conserved sequence (Wang et al., 2014).”
BackgroundInfluentialCanals, I., Quist, E., & Ahlenius, H. (2021) · Cellular Reprogramming · doi:10.1089/cell.2021.0045 · Cited by 11 · see citing works
- Authors
- Wang, J., Pol, S. U., Haberman, A. K., Wang, C., O’Bara, M. A., & Sim, F. J.
- Affiliations
- University at Buffalo, State University of New York (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-06-30
- Volume
- 111
- Issue
- 28
- Pages
- E2885-94
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4104854
- OpenAlex
- W2028561442
- Cited by
- 79
- References
- 48
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 1 · 2023: 5 · 2022: 13 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 1
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA016056)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- oligodendrocyte precursor cells, SOX10, transcription factors, oligodendrocyte differentiation, myelination, neural stem/progenitor cells, ASCL1, Nkx2.2, demyelinating disease, axon ensheathment, lentiviral overexpression
- MeSH terms
- Homeobox Protein Nkx-2.2, Animals, Cell Differentiation, Cells, Cultured, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Nuclear Proteins, Oligodendroglia, Transcription Factors, Transduction, Genetic, Lentivirus, Homeodomain Proteins, Stem Cell Transplantation, Mice, Neural Stem Cells, Transcriptome, Heterografts
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