Hair follicles (HFs) of mammalian epidermis are cycling throughout lifetime in order to continuously generate new hairs. Stem cells (SCs) residing in the bulge and hair germ fuel this cycle of hair regeneration that comprises three phases: (a) growth (anagen), where bulge and hair germ cells proliferate to generate the new hair shaft; (b) HF regression (catagen), where the HF keratinocytes undergo apoptosis and surviving cells move upwards to regenerate the hair germ and inner bulge; (c) resting (telogen), characterized by stem cell quiescence. Skin undergoes dramatic reshaping during catagen, yet mechanisms of cell death regulation during this phase are still not well understood. Here, we investigate the role of cell turnover and the impact of defective catagen on hair regeneration. In particular, we aimed to interfere with HF regression by overexpressing the anti-apoptotic protein Bcl-2 in murine epidermis (Bcl-2EOE mice), thereby blocking the mitochondrial apoptosis pathway. We show that Bcl-2EOE mice display a block in cell death during catagen after HF morphogenesis. Strikingly, the upward movement of the retracting strand was not affected. Instead, increased HF cell survival led to the formation of an enlarged bulge compartment, characterized by SC markers like SOX9 and Keratin 15, and a change in the architecture of the hair germ. As a consequence, the following hair regeneration cycle was impaired since mutant mice showed a delay in anagen entry and hair growth. Mechanistically, prolongation of telogen phase correlated with the upregulation of quiescence markers and a downregulation of activating signals. Taken together, our data demonstrate that a proper regulation of cell death during the hair cycle is required for the establishment and functioning of the HG and for the SC niche architecture. Importantly, our model will give new insights into mechanisms of cross talks between different cell types involved in catagen and into the process of SC activation during the regeneration cycle.

ESDR319 - Mechanisms of cell death regulation in hair regeneration

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING