Journal
CELL
Volume 161, Issue 5, Pages 1175-1186Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.04.001
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Funding
- National Key Basic Research Program of China [2011CBA01106, 2011CB965102, 2010CB945202, 2012CB966300, 2010CB945600, 2011CB966204, 2014CB964602]
- National Natural Foundation of China [91319309, 31271371, 81330030, 31271450, 31271375]
- NIH [P01 GM081621-01A1]
- Transcriptome and Epigenetics Core of Center for Study of Opioid Receptors and Drugs of Abuse (CSORDA center) [NIH-P50DA005010]
- Intellectual and Developmental Disabilities Research Center (IDDRC center) at the University of California, Los Angeles [NIH-P30HD004612]
- Yunnan and Shanghai local grants [2012HA013, 2014FC004, 13XD1403600, ZJ2014-ZD-002]
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The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.
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