Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain.
Wnt signaling
inflammation
interferon
modeling
neural stem cells
quiescence
sFRP5
simulations
single-cell transcriptomics
stem cell aging
subventricular zone
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
21
08
2018
revised:
12
11
2018
accepted:
24
01
2019
pubmed:
5
3
2019
medline:
7
1
2020
entrez:
5
3
2019
Statut:
ppublish
Résumé
The function of somatic stem cells declines with age. Understanding the molecular underpinnings of this decline is key to counteract age-related disease. Here, we report a dramatic drop in the neural stem cells (NSCs) number in the aging murine brain. We find that this smaller stem cell reservoir is protected from full depletion by an increase in quiescence that makes old NSCs more resistant to regenerate the injured brain. Once activated, however, young and old NSCs show similar proliferation and differentiation capacity. Single-cell transcriptomics of NSCs indicate that aging changes NSCs minimally. In the aging brain, niche-derived inflammatory signals and the Wnt antagonist sFRP5 induce quiescence. Indeed, intervention to neutralize them increases activation of old NSCs during homeostasis and following injury. Our study identifies quiescence as a key feature of old NSCs imposed by the niche and uncovers ways to activate NSCs to repair the aging brain.
Identifiants
pubmed: 30827680
pii: S0092-8674(19)30103-5
doi: 10.1016/j.cell.2019.01.040
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1419.e14Subventions
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.