title: Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche.
abstract: Adult neurogenic niches harbor quiescent neural stem cells; however, their in vivo identity has been elusive. Here, we prospectively isolate GFAP(+)CD133(+) (quiescent neural stem cells [qNSCs]) and GFAP(+)CD133(+)EGFR(+) (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro. In contrast, qNSCs are largely dormant in vivo, generate olfactory bulb interneurons with slower kinetics, and only rarely form colonies in vitro. Moreover, qNSCs are Nestin negative, a marker widely used for neural stem cells. Upon activation, qNSCs upregulate Nestin and EGFR and become highly proliferative. Notably, qNSCs and aNSCs can interconvert in vitro. Transcriptome analysis reveals that qNSCs share features with quiescent stem cells from other organs. Finally, small-molecule screening identified the GPCR ligands, S1P and PGD2, as factors that actively maintain the quiescent state of qNSCs.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Codega
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Silva-Vargas
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Maldonado-Soto
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA.
authors.forename: Annina M
authors.initials: AM
authors.lastname: Deleo
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Pastrana
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA; Department of Neurology, Columbia University, New York, NY 10032, USA; Department of Neuroscience, Columbia University, New York, NY 10032, USA; Department of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University, New York, NY 10032, USA; Motor Neuron Center, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA. Electronic address: fkd2101@cumc.columbia.edu.
authors.forename: Fiona
authors.initials: F
authors.lastname: Doetsch
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology*; D011446:Prospective Studies; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers