Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke.
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.
Carlén
Marie
M
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Meletis
Konstantinos
K
Göritz
Christian
C
Darsalia
Vladimer
V
Evergren
Emma
E
Tanigaki
Kenji
K
Amendola
Mario
M
Barnabé-Heider
Fanie
F
Yeung
Maggie S Y
MS
Naldini
Luigi
L
Honjo
Tasuku
T
Kokaia
Zaal
Z
Shupliakov
Oleg
O
Cassidy
Robert M
RM
Lindvall
Olle
O
Frisén
Jonas
J
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*
D006131:Growth Inhibitors; D051881:Receptor, Notch1