Inducing Hair Follicle Neogenesis with Secreted Proteins Enriched in Embryonic Skin

Organ development is a sophisticated process of self-organization. However, despite growing understanding of the developmental mechanisms, little is known about how to reactivate them postnatally for regeneration. We found that treatment of adult non-hair fibroblasts with cell-free extract from embryonic skin conferred upon them the competency to regenerate hair follicles. Proteomics analysis identified three secreted proteins enriched in the embryonic skin, apolipoprotein-A1, galectin-1 and lumican that together were essential and sufficient to induce new hair follicles. These 3 proteins show a stage-specific co-enrichment in the perifolliculogenetic embryonic dermis. Mechanistically, exposure to embryonic skin extract or to the combination of the 3 proteins altered the gene expression to an inductive hair follicle dermal papilla fibroblast-like profile and activated Igf and Wnt signaling, which are crucial for the regeneration process. Therefore, a cocktail of organ-specific extracellular proteins from the embryonic environment can render adult cells competent to re-engage in developmental interactions for organ neogenesis. Identification of factors that recreate the extracellular context of respective developing tissues can become an important strategy to promote regeneration in adult organs.