title: Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.
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.
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; College of Life Sciences, Nanchang University, Nanchang 330031, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Volkan
authors.initials: V
authors.lastname: Coskun
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Aibing
authors.initials: A
authors.lastname: Liang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Juehua
authors.initials: J
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Ge
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Zhanping
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Kunshan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Shanghai Stem Cell Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Life Sciences, Nanchang University, Nanchang 330031, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Cui
authors.affiliation: College of Life Sciences, Nanchang University, Nanchang 330031, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Lin
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Junbang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Tianjing Hospital, Tianjin Academy of Integrative Medicine, Tianjin 300211, China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: deVellis
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: 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.
authors.forename: Yi Eve
authors.initials: YE
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Siguang
authors.initials: S
authors.lastname: Li
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D004805:Ependyma / Q000166:cytology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors