Fan S.M.-Y.Tsai C.-F.Yen C.-M.MIAO-HSIA LINWang W.-H.CHIH-CHIEH CHANChen C.-L.Phua K.K.L.SZU-HUA PANPlikus M.V.SUNG-LIANG YUChen Y.-J.SUNG-JAN LIN2022-09-162022-09-1620180142-9612https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044122254&doi=10.1016%2fj.biomaterials.2018.03.003&partnerID=40&md5=c0e7ce602985b48f9eeaf7c7a0d00206https://scholars.lib.ntu.edu.tw/handle/123456789/620667Organ 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. © 2018 Elsevier Ltdenjournal article10.1016/j.biomaterials.2018.03.003295673882-s2.0-85044122254