Roles of Msx2 in Exogen Control: Modulating the Stem Cell Niche During the Transition from Hair Shedding to Regeneration [ATAC-Seq]

The exogen phase of the hair follicle cycle, during which club hairs are shed and new hairs emerge, represents a pivotal yet understudied transition marked by structural remodeling and cell fate changes. This study investigates the role of the transcription factor Msx2 in regulating hair anchoring, hair follicle stem cell (HFSC) lineage commitment, and extracellular matrix (ECM) remodeling during exogen. Using Msx2-knockout (KO) mice, we integrated transcriptomic, epigenomic, and functional assays to reveal Msx2 as a key regulator of exogen, critical for maintaining HFSC niche integrity, preserving bulge architecture, and coordinating lineage progression during hair regeneration. By modulating the balance between TGF-β and Wnt signaling pathways, Msx2 ensures proper HFSC activation and prevents premature epidermal differentiation and hair shedding. These findings provide mechanistic insights into the molecular control of hair cycling and highlight Msx2 dysfunction as a potential contributor to hair loss disorders, positioning it as a promising therapeutic target in regenerative dermatology.