title: Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.
abstract: Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain.
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Enric
authors.initials: E
authors.lastname: Llorens-Bobadilla
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Avni
authors.initials: A
authors.lastname: Baser
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Saiz-Castro
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Klara
authors.initials: K
authors.lastname: Zwadlo
authors.affiliation: Molecular Neurobiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. Electronic address: a.martin-villalba@dkfz.de.
authors.forename: Ana
authors.initials: A
authors.lastname: Martin-Villalba
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D020869:Gene Expression Profiling / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology*; D059010:Single-Cell Analysis / Q000379:methods*; D014158:Transcription, Genetic
chemical_list: D007371:Interferon-gamma