Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects
Open accessAbstract
Human embryonic stem cells (hESCs) offer a platform to bridge what we have learned from animal studies to human biology. Using oligodendrocyte differentiation as a model system, we show that sonic hedgehog (SHH)-dependent sequential activation of the transcription factors OLIG2, NKX2.2 and SOX10 is required for sequential specification of ventral spinal OLIG2-expressing progenitors, pre-oligodendrocyte precursor cells (pre-OPCs) and OPCs from hESC-derived neuroepithelia, indicating that a conserved transcriptional network underlies OPC specification in human as in other vertebrates. However,the transition from pre-OPCs to OPCs is protracted. FGF2, which promotes mouse OPC generation, inhibits the transition of pre-OPCs to OPCs by repressing SHH-dependent co-expression of OLIG2 and NKX2.2. Thus, despite the conservation of a similar transcriptional network across vertebrates, human stem/progenitor cells may respond differently to those of other vertebrates to certain extrinsic factors.
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Robust protocols exist for differentiating human ES or iPS cells into neurons, astrocytes and oligodendrocytes.
“Robust protocols have been developed to induce human ES or iPS cells to differentiate into the different neuroectodermal cell types of the CNS including neurons, astrocytes and oligodendrocytes 7,8.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [7]
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References 53 · Cited by 169
- Authors
- Hu, B.-Y., Du, Z.-W., Li, X.-J., Ayala, M., & Zhang, S.-C.
- Affiliations
- Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, 1500 Highland Avenue,Madison, WI 53705, USA.
- University of Wisconsin–Madison (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-05-01
- Volume
- 136
- Issue
- 9
- Pages
- 1443-1452
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2674255
- OpenAlex
- W1994285313
- Cited by
- 169
- References
- 53
- Citations by year
- 2026: 2 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 10 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 11 · 2016: 22 · 2015: 21 · 2014: 13 · 2013: 16 · 2012: 16
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS045926)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD03352., P30HD003352)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- oligodendrocyte differentiation, human embryonic stem cells, Sonic hedgehog signaling, Olig2, Nkx2.2, SOX10, FGF2, oligodendrocyte precursor cells, transcriptional regulatory networks, neuroepithelium
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Homeobox Protein Nkx-2.2, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Humans, Microscopy, Electron, Myelin Sheath, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Oligodendroglia, Transcription Factors, Signal Transduction, Fibroblast Growth Factor 2, Homeodomain Proteins, Zebrafish Proteins, Basic Helix-Loop-Helix Proteins, Embryonic Stem Cells, Hedgehog Proteins
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