title: Single-Cell Transcriptomic Analysis Defines Heterogeneity and Transcriptional Dynamics in the Adult Neural Stem Cell Lineage.
abstract: Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here, we use single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs. Finally, using the power of single-cell profiling, we conduct a meta-analysis to compare in vivo NSCs and in vitro cultures, distinct fluorescence-activated cell sorting strategies, and different neurogenic niches. These data provide a resource for the field and contribute to an integrative understanding of the adult NSC lineage.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ben W
authors.initials: BW
authors.lastname: Dulken
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Dena S
authors.initials: DS
authors.lastname: Leeman
authors.affiliation: Fluidigm Corporation, South San Francisco, CA 94080, USA.
authors.forename: Stéphane C
authors.initials: SC
authors.lastname: Boutet
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Katja
authors.initials: K
authors.lastname: Hebestreit
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford University, Stanford University, Stanford, CA 94305, USA. Electronic address: abrunet1@stanford.edu.
authors.forename: Anne
authors.initials: A
authors.lastname: Brunet
mesh_terms: D000465:Algorithms; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D025341:Principal Component Analysis; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018031:Connexin 43; C088334:Distal-less homeobox proteins; C543076:GJA1 protein, mouse; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; D014157:Transcription Factors; D012313:RNA; C401838:Atp1a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
keywords: adult neurogenesis; machine learning; neural stem cells; pseudotemporal ordering; single-cell RNA-seq