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| Status |
Public on Feb 01, 2011 |
| Title |
Complementary patterns of gene expression by human oligodendrocyte progenitors and their environment predict determinants of progenitor maintenance and differentiation. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
OBJECTIVE: Glial progenitor cells are abundant in adult human white matter. This study was designed to identify signaling pathways regulating their self-renewal and fate.
METHODS: We compared the transcriptional profiles of freshly sorted adult human white matter progenitor cells (WMPCs), purified by A2B5-based immunomagnetic sorting, with those of the white matter from which they derived.
RESULTS: We identified 132 genes differentially expressed by WMPCs; these included principal components of five receptor-defined signaling pathways, represented by platelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FGFR3), receptor tyrosine phosphatase-beta/zeta (RTPZ), notch, and syndecan3. WMPCs also differentially expressed the bone morphogenetic protein 4 (BMP4) inhibitors neuralin and BAMBI (BMP and activin membrane-bound inhibitor), suggesting tonic defense against BMP signaling. Differential overexpression of RTPZ was accompanied by that of its modulators pleiotrophin, NrCAM, tenascin, and the chondroitin sulfate proteoglycans, suggesting the importance of RTPZ signaling to WMPCs. When exposed to the RTPZ inhibitor bpV(phen), or lentiviral-shRNAi against RTPZ, WMPCs differentiated as oligodendrocytes. Conversely, when neuralin and BAMBI were antagonized by BMP4, astrocytic differentiation was induced, which was reversible by noggin.
INTERPRETATION: The RTPZ and BMP pathways regulate the self-maintenance of adult human WMPCs, and can be modulated to induce their oligodendrocytic or astrocytic differentiation. As such, they provide targets by which to productively mobilize resident progenitor cells of the adult human brain.
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| Overall design |
6 samples, three biological replicates (individual patients), 2 groups (A2B5+ and unsorted cells).
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| Contributor(s) |
Sim FJ, Lang JK, Waldau B, Schwartz TE, Pilcher WH, Chandross KJ, Natesan S, Merrill JE, Goldman SA |
| Citation(s) |
16634042 |
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| Submission date |
Jan 10, 2011 |
| Last update date |
Dec 13, 2018 |
| Contact name |
Fraser James Sim |
| E-mail(s) |
fjsim@buffalo.edu
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| Phone |
7168292151
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| Organization name |
University at Buffalo
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| Department |
Pharmacology
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| Street address |
3435 Main Street
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14216 |
| Country |
USA |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA136657 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26535_RAW.tar |
42.1 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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