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.
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We are grateful to U. Lendahl, O. Hermanson, A. Simon and members of the Frisén laboratory for valuable discussions; L. Ostrowski for the Foxj1 promoter construct; T. Li for antibodies to Crocc; U. Lendahl for N1IC and 12× Rbpj-dsgfp cDNA; O. Bergmann for virus injections; and M-L. Spångberg and K. Hamrin for technical assistance. This study was supported by grants from the Swedish Research Council, the Swedish Cancer Society, the Foundation for Strategic Research, the Juvenile Diabetes Research Foundation, the Karolinska Institute, Tobias Stiftelsen and the European Commission Framework VI Programme, EuroStemCell and StemStroke. M.C. and E.E. are supported by postdoctoral fellowships from the Swedish Brain Foundation (Hjärnfonden), C.G. by a postdoctoral fellowship from the Wenner-Gren Foundation and F.B.-H. by postdoctoral fellowships from the Canadian Institutes of Health Research and the Christopher and Dana Reeve Foundation.
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Carlén, M., Meletis, K., Göritz, C. et al. Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci 12, 259–267 (2009). https://doi.org/10.1038/nn.2268
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