Hair Follicle Terminal Differentiation Is Orchestrated by Distinct Early and Late Matrix Progenitors

During development and regeneration, matrix progenitors undergo terminal differentiation to form the concentric layers of the hair follicle. These differentiation events are thought to require signals from the mesenchymal dermal papilla (DP); however, it remains unclear how DP-progenitor cell interactions govern specific cell fate decisions. Here, we show that the hair follicle differentiated layers are specified asynchronously, with early matrix progenitors initiating differentiation before surrounding the DP. Furthermore, these early matrix cells can undergo terminal differentiation in the absence of Shh, BMP signaling, and DP maturation. Whereas early matrix progenitors form the hair follicle companion layer, later matrix populations progressively form the inner root sheath and hair shaft. Altogether, our findings characterize some of the earliest terminal differentiation events in the hair follicle and reveal that the matrix progenitor pool can be divided into early and late phases based on distinct temporal, molecular, and functional characteristics.