Universität zu Köln

Geueke, Anna, Mantellato, Giada, Kuester, Florian, Schettina, Peter, Nelles, Melanie, Seeger, Jens Michael, Kashkar, Hamid ORCID: 0000-0003-2796-1429 and Niemann, Catherin (2021). The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function. EMBO Rep., 22 (10). HOBOKEN: WILEY. ISSN 1469-3178

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Geueke, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Mantellato, Giada UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuester, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schettina, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nelles, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Jens Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED orcid.org/0000-0003-2796-1429 UNSPECIFIED Niemann, Catherin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-569751
DOI:	10.15252/embr.202052301
Journal or Publication Title:	EMBO Rep.
Volume:	22
Number:	10
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-3178
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LABEL-RETAINING CELLS; ABT-199; NICHE; DEATH; DIFFERENTIATION; PROLIFERATION; MAINTAINS; CYCLE; QUIESCENCE; IDENTITY Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56975