title: Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone.
abstract: Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to probe heterogeneity of the postnatal SVZ, we microdissected its dorsal and lateral walls at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors (loss-of-function or ectopic gain-of-function in vivo) influenced NSC specification indicating that the fate of regionalized postnatal SVZ-NSCs can be readily modified. These findings reveal the pronounced transcriptional heterogeneity of the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Stem Cells 2015;33:2232-2242.
authors.affiliation: Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: Kasum
authors.initials: K
authors.lastname: Azim
authors.affiliation: Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: Anahí
authors.initials: A
authors.lastname: Hurtado-Chong
authors.affiliation: Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: Nitin
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Inserm U846, Stem Cell and Brain Research Institute, Université de Lyon, Université Lyon 1, Bron, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zweifel
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Verdon
authors.initials: V
authors.lastname: Taylor
authors.affiliation: Brain Research Institute, University of Zurich/ETH Zurich, Zurich, Switzerland.|Inserm U846, Stem Cell and Brain Research Institute, Université de Lyon, Université Lyon 1, Bron, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Raineteau
mesh_terms: D000818:Animals; D015870:Gene Expression; D020547:Lateral Ventricles / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D055153:Stem Cell Niche / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome / Q000502:physiology
chemical_list: D014157:Transcription Factors
keywords: Fate specification; Neural stem cell; Postnatal neurogenesis; Regionalization; Subventricular zone; Transcriptome