MCL‑1 is essential for hair growth by preventing BAK‑mediated apoptosis of activated adult hair follicle stem cells. MCL‑1 is essential for hair growth by preventing BAK‑mediated apoptosis of activated adult hair follicle stem cells

Hair follicles (HFs) cycle between expansion, regression and quiescence. To investigate the role of MCL-1, a BCL-2 family protein with anti-apoptotic and non-apoptotic functions in this dynamic process, we delete Mcl-1 within the skin epithelium, using both constitutive and inducible systems. Mcl-1 deletion does not impair HF organogenesis but results in gradual hair loss and HF stem cells (HFSC) elimination. Single-cell RNA-seq profiling unveils activated DNA repair and P53 signaling pathways in HFSCs during hair regeneration. Acute Mcl-1 deletion led to the depletion of activated HFSCs. Moreover, the ERBB pathway is found to promote MCL-1 protein expression in HFs. Accordingly, ERBB inhibition depletes activated HFSCs in adult mice. Remarkably, the loss of a single Bak allele rescues Mcl-1 deletion-associated defects in both HFs and mammary glands. These findings emphasize the pivotal role of MCL-1 in inhibiting proliferation stress-induced apoptosis when quiescent stem cells re-enter cell cycling to fuel tissue regeneration. Overall design: Single-cell RNA-seq profiling on the dynamics of adult hair follicles regeneration at 0-hour, 4-hour, 16-hour, 2-day, 4-day, and 6-day post depilation.