The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function.
Bcl-2
Lef1
apoptosis
hair follicle
stem cell
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 10 2021
05 10 2021
Historique:
revised:
08
07
2021
received:
18
12
2020
accepted:
13
07
2021
pubmed:
4
8
2021
medline:
1
6
2022
entrez:
3
8
2021
Statut:
ppublish
Résumé
Maintaining the architecture, size and composition of an intact stem cell (SC) compartment is crucial for tissue homeostasis and regeneration throughout life. In mammalian skin, elevated expression of the anti-apoptotic Bcl-2 protein has been reported in hair follicle (HF) bulge SCs (BSCs), but its impact on SC function is unknown. Here, we show that systemic exposure of mice to the Bcl-2 antagonist ABT-199/venetoclax leads to the selective loss of suprabasal BSCs (sbBSCs), thereby disrupting cyclic HF regeneration. RNAseq analysis shows that the pro-apoptotic BH3-only proteins BIM and Bmf are upregulated in sbBSCs, explaining their addiction to Bcl-2 and the marked susceptibility to Bcl-2 antagonism. In line with these observations, conditional knockout of Bcl-2 in mouse epidermis elevates apoptosis in BSCs. In contrast, ectopic Bcl-2 expression blocks apoptosis during HF regression, resulting in the accumulation of quiescent SCs and delaying HF growth in mice. Strikingly, Bcl-2-induced changes in size and composition of the HF bulge accelerate tumour formation. Our study identifies a niche-instructive mechanism of Bcl-2-regulated apoptosis response that is required for SC homeostasis and tissue regeneration, and may suppress carcinogenesis.
Identifiants
pubmed: 34342114
doi: 10.15252/embr.202052301
pmc: PMC8490995
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
Banques de données
GEO
['GSE166921']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e52301Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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