A role for TGF-beta in oligodendrocyte differentiation.
Open accessAbstract
Oligodendrocyte-type-2 astrocyte (O-2A) glial progenitor cells undergo a limited number of mitotic divisions in response to PDGF before differentiating into oligodendrocytes, the myelin-forming cell of the CNS. We examined the mechanism limiting O-2A proliferation, and demonstrate that these cells secrete an inhibitor of cell proliferation that can be neutralized with antibodies to TGF-beta. O-2A cells also secrete an inhibitory activity that cannot be neutralized with TGF-beta antibodies. O-2A progenitor cultures express TGF-beta 1 isoform and its transcript, while oligodendrocyte cultures express TGF-beta 1, beta-2, and beta-3 isoforms. Both recombinant TGF-beta 1 and O-2A conditioned medium inhibit the proliferation of O-2A progenitor cells cultured in the presence of PDGF, and this inhibition can be partially neutralized with polyclonal TGF-beta antibodies. Thus, TGF-beta produced by O-2A cells may limit PDGF-driven mitosis and promote oligodendrocyte development. TGF-beta is a less potent inhibitor of O-2A proliferation when these cells are cultured in the presence of bFGF, suggesting that bFGF interferes with TGF-beta signaling. Thus, the production of TGF-beta by cells in the O-2A lineage may account for the distinct effects of PDGF and bFGF on O-2A progenitor cell proliferation. Moreover, our results suggest that TGF-beta may be an important mediator of oligodendrocyte differentiation.
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TGFβ isoforms induce myelin protein expression.
“Additionally, TGFβ isoforms have been shown to induce myelin protein expression42, 43.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [43]
The Results report that recombinant TGF-β1 increased the proportion of cultured O-2A cells expressing galactocerebroside, a marker of oligodendrocyte differentiation (Fig. 8). Galactocerebroside is not a protein, and the passages do not show that TGF-β isoforms induce myelin protein expression. The isoform-expression Results (p. 1399) identify TGF-β2 and TGF-β3 in oligodendrocytes but do not test their effect on myelin proteins. (LLM, conf=0.87)
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M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
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Remyelinating and neuroprotective treatments in multiple sclerosis
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- Authors
- McKinnon, R. D., Piras, G., Ida, J. A., & Dubois-Dalcq, M.
- Affiliations
- Division of Neurosurgery, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
- ORCID
- McKinnon, R D
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1993-06-15
- Volume
- 121
- Issue
- 6
- Pages
- 1397-1407
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2119703
- OpenAlex
- W1992172737
- Cited by
- 248
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 13 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- TGF-beta, oligodendrocyte differentiation, cell proliferation inhibition, platelet-derived growth factor, basic fibroblast growth factor, TGF-beta isoforms, myelination, conditioned medium, TGF-beta signaling
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Base Sequence, Cell Differentiation, Cell Division, Cells, Cultured, Immunohistochemistry, Molecular Sequence Data, Oligodendroglia, RNA, Messenger, Transforming Growth Factor beta, Rats, Sprague-Dawley, Rats
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