title: Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke.
abstract: Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.
authors.affiliation: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Carlén
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Meletis
authors.forename: Christian
authors.initials: C
authors.lastname: Göritz
authors.forename: Vladimer
authors.initials: V
authors.lastname: Darsalia
authors.forename: Emma
authors.initials: E
authors.lastname: Evergren
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanigaki
authors.forename: Mario
authors.initials: M
authors.lastname: Amendola
authors.forename: Fanie
authors.initials: F
authors.lastname: Barnabé-Heider
authors.forename: Maggie S Y
authors.initials: MS
authors.lastname: Yeung
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
authors.forename: Oleg
authors.initials: O
authors.lastname: Shupliakov
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cassidy
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.forename: Jonas
authors.initials: J
authors.lastname: Frisén
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004805:Ependyma / Q000166:cytology / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D051881:Receptor, Notch1 / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006131:Growth Inhibitors; D051881:Receptor, Notch1