Jiang Chen, Centonze Alessia, Song Yura, Chrisnandy Antonius, Tika Elisavet, Rezakhani Saba, Zahedi Zahra, Bouvencourt Gaëlle, Dubois Christine, Van Keymeulen Alexandra, Lütolf Matthias, Sifrim Alejandro, Blanpain Cédric
Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Nat Commun. 2024 Dec 18;15(1):10482. doi: 10.1038/s41467-024-54843-5.
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.
腺上皮，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，腺上皮起源于多能干细胞（SCs），出生后被单能基底干细胞和单能管腔干细胞取代。不同的条件，如基底细胞移植、管腔细胞消融和癌基因表达，可在不同的腺上皮中重新诱导成年基底干细胞（BaSCs）的多能性。调节多能性重新激活的机制尚不完全清楚。在这里，我们发现，在不同的多能条件下，BaSCs中I型胶原蛋白的表达通常会上调。增加胶原蛋白浓度或细胞外基质（ECM）的硬度可促进MG和前列腺类器官中BaSC的多能性。在坚硬条件下对MG类器官进行单细胞RNA测序，揭示了β1整合素/FAK/AP-1轴在调节BaSC多能性中的重要性。总之，我们的研究揭示了胶原蛋白信号和ECM硬度在调节腺上皮多能性中的关键作用。
