Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke

Marie Carlén, Konstantinos Meletis, Christian Göritz, Vladimer Darsalia, Emma Evergren, Kenji Tanigaki, Mario Amendola, Fanie Barnabé-Heider, Maggie S Y Yeung, Luigi Naldini, Tasuku Honjo, Zaal Kokaia, Oleg Shupliakov, Robert M. Cassidy, Olle Lindvall, Jonas Frisén

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalNature Neuroscience
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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