The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function
| Autor: | Catherin Niemann, Florian Kuester, Peter Schettina, Giada Mantellato, Hamid Kashkar, Anna Geueke, Melanie Nelles, Jens M. Seeger |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.disease_cause
Biochemistry Article Mice Downregulation and upregulation Conditional gene knockout Genetics medicine Animals Lef1 Molecular Biology Tissue homeostasis Skin Cancer hair follicle Chemistry Regeneration (biology) Stem Cells Bcl‐2 Stem Cells & Regenerative Medicine apoptosis Articles Hair follicle Cell biology stem cell medicine.anatomical_structure Apoptosis Autophagy & Cell Death Stem cell Carcinogenesis Apoptosis Regulatory Proteins |
| Zdroj: | EMBO Reports |
| ISSN: | 1469-3178 |
| Popis: | 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. Anti‐apoptotic Bcl‐2 protein function is required to maintain a hair follicle subpopulation of stem cells in murine skin. Blocking cell death by Bcl‐2 overexpression affects the hair follicle stem cell niche and hair follicle regeneration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text