Stem cell renewal and differentiation are regulated by interactions with the niche. Although multiple cell populations have been identified in distinct anatomical compartments, little is known about niche-specific molecular factors. Using skin as a model system and combining single-cell RNA-seq data analysis, immunofluorescence, and transgenic mouse models, we show that the transmembrane protein embigin is specifically expressed in the sebaceous gland and that the number of embigin-expressing cells is negatively regulated by Wnt. The loss of embigin promotes exit from the progenitor compartment and progression toward differentiation, and also compromises lipid metabolism. Embigin modulates sebaceous niche architecture by affecting extracellular matrix organization and basolateral targeting of monocarboxylate transport. We discover through ligand screening that embigin is a direct fibronectin receptor, binding to the N-terminal fibronectin domain without impairing integrin function. Our results solve the long-standing question of how embigin regulates cell adhesion and demonstrate a mechanism that couples adhesion and metabolism.

干细胞更新和分化是通过与生态位的相互作用来调节的。尽管已在不同的解剖区室中鉴定出多个细胞群，但人们对生态位特异性分子因子知之甚少。以皮肤为模型系统，结合单细胞RNA-seq数据分析、免疫荧光和转基因小鼠模型，我们发现跨膜蛋白embigin在皮脂腺中特异性表达，并且embigin表达细胞的数量受到负调控由Wnt。 Embigin 的缺失促进祖细胞室的退出和分化的进展，并且还会损害脂质代谢。 Embigin 通过影响细胞外基质组织和单羧酸盐转运的基底外侧靶向来调节皮脂腺生态位结构。我们通过配体筛选发现embigin是一种直接的纤连蛋白受体，与N端纤连蛋白结构域结合而不损害整合素功能。我们的结果解决了 Embigin 如何调节细胞粘附这一长期存在的问题，并证明了粘附和代谢的耦合机制。