Functional Genomic Analysis of Oligodendrocyte Differentiation
Open accessAbstract
To better understand the molecular mechanisms governing oligodendrocyte (OL) differentiation, we have used gene profiling to quantitatively analyze gene expression in synchronously differentiating OLs generated from pure oligodendrocyte precursor cells in vitro. By comparing gene expression in these OLs to OLs generated in vivo, we discovered that the program of OL differentiation can progress normally in the absence of heterologous cell-cell interactions. In addition, we found that OL differentiation was unexpectedly prolonged and occurred in at least two sequential stages, each characterized by changes in distinct complements of transcription factors and myelin proteins. By disrupting the normal dynamic expression patterns of transcription factors regulated during OL differentiation, we demonstrated that these sequential stages of gene expression can be independently controlled. We also uncovered several genes previously uncharacterized in OLs that encode transmembrane, secreted, and cytoskeletal proteins that are as highly upregulated as myelin genes during OL differentiation. Last, by comparing genomic loci associated with inherited increased risk of multiple sclerosis (MS) to genes regulated during OL differentiation, we identified several new positional candidate genes that may contribute to MS susceptibility. These findings reveal a previously unexpected complexity to OL differentiation and suggest that an intrinsic program governs successive phases of OL differentiati…
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A complete transcriptome dataset that allows direct comparison of gene expression across all major glial and vascular brain cell types is lacking.
“a complete transcriptome dataset that allows direct comparison of gene expression across all of the major glial and vascular brain cell types is lacking.”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Dugas et al., 2006
Some oligodendrocyte-lineage markers are expressed in a graded manner at high levels during one maturation stage and at lower levels at a different maturation stage.
“As expected, some of the oligodendrocyte-lineage markers are expressed in a graded manner at high levels during one maturation stage and at lower levels at a different maturation stage (see OPC, NFO, and MO data in Fig. 1D; Dugas et al., 2006).”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Dugas et al., 2006
Bin1 is among the top 50 highly expressed genes in cultured oligodendrocytes by genomic analysis.
“Although it has been generally assumed that BIN1 is mainly expressed in neurons, Bin1 was found among the top 50 highly expressed genes in cultured oligodendrocytes by genomic analysis [32].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [32]
These findings corroborate previous studies that reported high levels of Bin1 transcripts in mature oligodendrocytes.
“These findings corroborated previous studies that reported high levels of Bin1 transcripts in mature oligodendrocytes [32, 45] and are entirely in agreement with our in vivo localization of BIN1 and Amphiphysin 1 in mature oligodendrocytes and neurons, respectively, by immunohistochemical staining.”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [32]
Bin1 is among the top 50 highly expressed genes in cultured oligodendrocytes in a microarray study.
“the Barres lab’s identification of Bin1 among the top 50 highly expressed genes in cultured oligodendrocytes in a microarray study [32]”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [32]
Three recent studies also support the active transcription of PMP22 in oligodendrocytes.
“Of note, three recent studies also support the active transcription of PMP22 in oligodendrocytes (Dugas et al., 2006; Nielsen et al., 2006; Sohn et al., 2006).”
From Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes (2008) · cites this paper as Dugas et al., 2006
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References 71 · Cited by 324
- Authors
- Dugas, J. C., Tai, Y. C., Speed, T. P., Ngai, J., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- University of California, Berkeley (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-10-25
- Volume
- 26
- Issue
- 43
- Pages
- 10967-10983
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674672
- OpenAlex
- W2061556393
- Cited by
- 324
- References
- 71
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 7 · 2022: 11 · 2021: 22 · 2020: 13 · 2019: 15 · 2018: 18 · 2017: 15 · 2016: 23 · 2015: 20 · 2014: 18 · 2013: 27 · 2012: 19
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Myelin Repair Foundation
- Multiple Sclerosis Society
- National Institutes of Health (5r01mh061665-03)
- National Institute of Mental Health (R01 MH61665)
- National Human Genome Research Institute (HG0047, K22HG000047, T32HG000047)
- National Eye Institute (R01EY010257, R01 EY10257)
- National Institute on Deafness and Other Communication Disorders (R01DC007235)
- U.S. National Library of Medicine (R01 LM07609-01, R01LM007609)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD061665)
- 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 › Developmental Biology and Gene Regulation
- Keywords
- oligodendrocyte differentiation, oligodendrocyte precursor cells, gene expression profiling, transcription factors, myelin proteins, cell-cell interactions, positional candidate genes, axonal myelination, transmembrane proteins, secreted proteins, cytoskeletal proteins
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Oligodendroglia, Transcription Factors, Rats, Sprague-Dawley, Oligonucleotide Array Sequence Analysis, Protein Array Analysis, Quantitative Trait Loci, Rats
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