MafB regulates hair follicle stem cell activation and hair regeneration through NFATc1 signaling pathway.

Alopecia, a prevalent condition driven by abnormal hair follicle cycling and stem cell (HFSCs) dysregulation, underscores the need to elucidate molecular mechanisms governing HFSCs activation. While the nuclear factor of activated T cells c1 (NFATc1) is known to maintain HFSCs quiescence by suppressing cyclin-dependent kinase 4 (CDK4), the upstream regulators of this pathway remain unclear. Here, we identify MafB as a key modulator of HFSCs dynamics through NFATc1 signaling. Transcriptome sequencing of murine skin revealed elevated MafB expression during active hair regeneration. Adenoviral overexpression of MafB in depilated mice accelerated hair regrowth, increased hair follicle diameter, and enhanced HFSCs proliferation. Conversely, MafB knockdown suppressed regeneration and reduced the prolifiration ability of HFSCs. In vitro, MafB overexpression promoted HFSCs proliferation, migration, and differentiation, while mechanistic studies demonstrated MafB inhibits NFATc1 transcription, thereby relieving CDK4 repression and activating Wnt/β-catenin signaling. Rescue experiments confirmed NFATc1 restoration abrogated MafB-induced HFSCs activation. These findings establish MafB as a critical regulator of hair follicle cycling through the NFATc1/CDK4 axis, offering novel therapeutic avenues for alopecia.