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Cell. 2015 May 21;161(5):1175-1186. doi: 10.1016/j.cell.2015.04.001.

Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

Author information

1
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; College of Life Sciences, Nanchang University, Nanchang 330031, China.
2
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
3
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
4
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
5
Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
6
College of Life Sciences, Nanchang University, Nanchang 330031, China.
7
Tianjing Hospital, Tianjin Academy of Integrative Medicine, Tianjin 300211, China.
8
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
9
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China. Electronic address: yi.eve.sun@gmail.com.
10
Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China. Electronic address: siguangli@163.com.

Abstract

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.

PMID:
26000486
PMCID:
PMC4851109
DOI:
10.1016/j.cell.2015.04.001
[Indexed for MEDLINE]
Free PMC Article

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