Glandular epithelia, including mammary gland (MG) and prostate, are composed of luminal and basal cells. During embryonic development, glandular epithelia arise from multipotent stem cells (SCs) that are replaced after birth by unipotent basal and unipotent luminal SCs. Different conditions, such as basal cell transplantation, luminal cell ablation, and oncogene expression can reinduce adult basal SC (BaSCs) multipotency in different glandular epithelia. The mechanisms regulating the reactivation of multipotency are incompletely understood. Here, we have found that Collagen I expression is commonly upregulated in BaSCs across the different multipotent conditions. Increasing collagen concentration or stiffness of the extracellular matrix (ECM) promotes BaSC multipotency in MG and prostate organoids. Single cell RNA-seq of MG organoids in stiff conditions have uncovered the importance of β1 integrin/FAK/AP-1 axis in the regulation of BaSC multipotency. Altogether our study uncovers the key role of Collagen signaling and ECM stiffness in the regulation of multipotency in glandular epithelia.

腺体上皮细胞，包括乳腺 （MG） 和前列腺，由管腔细胞和基底细胞组成。在胚胎发育过程中，腺上皮细胞起源于多能干细胞 （SCs），这些干细胞在出生后被单能基础和单能管腔 SCs 取代。不同的情况，如基底细胞移植、管腔细胞消融和癌基因表达，可以在不同的腺体上皮细胞中再诱导成人基础 SC （BaSCs） 多能性。调节多能性再激活的机制尚不完全清楚。在这里，我们发现胶原蛋白 I 的表达通常在不同的多能条件下的 BaSCs 中上调。增加细胞外基质 （ECM） 的胶原蛋白浓度或刚度可促进 MG 和前列腺类器官中的 BaSC 多能性。在刚性条件下 MG 类器官的单细胞 RNA-seq 揭示了 β1 整合素/FAK/AP-1 轴在调节 BaSC 多能性中的重要性。总而言之，我们的研究揭示了胶原蛋白信号传导和 ECM 刚度在腺上皮细胞多能性调节中的关键作用。