Lineage-Committed Fibroblast Populations Are More Efficient at Regenerating Hair Follicles in Chamber Grafting Assays Compared to Undifferentiated Embryonic Fibroblasts

The study investigated the ability of fibroblasts at different developmental stages to support hair follicle formation using chamber grafting assays. Contrary to the initial hypothesis, E14.5 undifferentiated embryonic fibroblasts did not support de novo hair follicle formation, while E17.5 and P5 fibroblasts, which were more differentiated, did. This suggested that fibroblasts become more efficient at regenerating hair follicles after they are lineage-committed post-E16.5. Single-cell RNA sequencing showed that E14.5 fibroblasts were undifferentiated with a precursor-like molecular signature, whereas E17.5 and P5 fibroblasts displayed diverse and defined molecular signatures. The findings highlighted the importance of fibroblast differentiation in hair follicle regeneration and suggested that understanding these mechanisms could aid in developing regenerative therapies for adult skin injuries.