The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function.

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.

Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies.

Sebaceous glands (SGs), typically associated with hair follicles, are critical for the homeostasis and function of mammalian skin. The main physiological function of SGs is the production and holocrine secretion of sebum to lubricate and protect the skin. Defective SGs have been linked to a variety of skin disorders, including acne, seborrheic dermatitis and formation of sebaceous tumors. Thus, a better understanding how SGs are formed and maintained is important to unravel the underlying molecular and cellular mechanisms of SG pathologies and to find better and effective therapies. Over the last two decades, research has come a long way from the initial identification of skin epithelial stem cells to the isolation and functional characterization of multiple stem cell pools as well as a better understanding of their unique and complex activities that drive skin homeostasis and operate in skin pathologies. Here, we discuss recent progress in unravelling cellular mechanisms underlying SG development, homeostasis and sebaceous tumor formation and assess the role of stem and progenitor cells in controlling SG physiology and disease processes. The development of elegant in vivo imaging as well as various in vitro and ex vivo stem cell and SG tissue models will advance mechanistic studies on SG function and allow drug screening and testing for efficient and successful targeting SG pathologies.