ALKBH5 acts as a facilitator for hair follicle telogen to anagen transition

Hair cycle transitions play a pivotal role in sustaining hair growth, particularly the switch from telogen to anagen. During this process, hair follicle stem cells (HFSCs) are regulated by a complex and dynamic niche of signals that drive the cell state from quiescence to activation. However, how HFSCs adjust their state to respond to these signals remains unclear. Here, we show that Alkbh5 expression is downregulated during late telogen, and its deletion promotes HFSC activation and proliferation, accelerating the telogen–anagen transition in mice. In vitro, ALKBH5-deficient HFSCs display enhanced proliferation under 3D culture. Loss of ALKBH5 increases the m6A methylation of Mcam, which is subsequently recognized and bound by YTHDF1, thereby stabilizing Mcam mRNA. Mcam expression increases as Alkbh5 decreases during late telogen, and Mcam knockdown impairs HFSC proliferation, potentially through reduced Wnt responsiveness. Furthermore, Mettl3 is also involved in maintaining hair cycle progression. We conclude that ALKBH5, a facilitator for hair cycle transition, dynamically regulates Mcam expression mediated by m6A methylation, and that proper HFSC activation potentially requires a balanced m6A regulatory mechanism involving both ALKBH5 and METTL3.