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.

器官发育是一个复杂的自我组织过程。然而，尽管对发育机制的理解日益加深，但对于如何在出生后重新激活它们以进行再生知之甚少。我们发现，用来自胚胎皮肤的无细胞提取物处理成年的非毛发成纤维细胞，可以赋予它们再生毛囊的能力。蛋白质组学分析确定了在胚胎皮肤中富集的三种分泌蛋白，载脂蛋白A1，半乳糖凝集素1和Lumican，它们共同构成诱导新毛囊的必要条件和充分条件。这3种蛋白在毛囊形成胚胚胎真皮中显示出阶段特异性共富集。机械上，暴露于胚胎皮肤提取物或3种蛋白质的组合将基因表达改变为诱导性毛囊，真皮乳头成纤维细胞样特征以及激活的Igf和Wnt信号传导，这对于再生过程至关重要。因此，来自胚胎环境的器官特异性细胞外蛋白混合物可以使成年细胞有能力重新参与器官新生的发育相互作用。鉴定重建各个发育中组织的细胞外环境的因素可以成为促进成年器官再生的重要策略。来自胚胎环境的器官特异性细胞外蛋白混合物可以使成年细胞有能力重新参与器官新生的发育相互作用。鉴定重建各个发育中组织的细胞外环境的因素可以成为促进成年器官再生的重要策略。来自胚胎环境的器官特异性细胞外蛋白混合物可以使成年细胞有能力重新参与器官新生的发育相互作用。鉴定重建各个发育中组织的细胞外环境的因素可以成为促进成年器官再生的重要策略。