芬兰赫尔辛基大学Sara A. Wickström等研究人员合作发现，跨区机械力协调细胞形状和命运转变来生成组织结构。2024年2月1日，《自然—细胞生物学》杂志在线发表了这项成果。

研究人员确定了上皮细胞和间充质细胞间的收缩、增殖和蛋白分解活动所产生的协调机械力在基板结构形成过程中的关键作用。成纤维细胞环逐渐包裹着基板细胞，产生向心收缩力，这种收缩力与极化上皮肌球蛋白活性共同作用，促进了基板细胞的伸长和局部组织的增厚。这些机械应力进一步加强了Sox9的分区表达，促进干细胞定位。

随后，蛋白水解重塑使基底膜局部软化，从而释放对基板的压力，使局部细胞分裂、组织流动化和上皮侵入底层间质。这些实验和建模共同确定了细胞形状的动态转变和组织尺度的机械合作是协调器官形成的关键因素。

据了解，形态发生和细胞状态转换必须在时间和空间上相互协调，才能产生功能性组织。哺乳动物的毛囊发育是了解这些过程耦合的绝佳范例。毛囊发育始于上皮内陷的形成，即基板，与指定的毛囊干细胞群的出现相吻合。指导上皮变形、细胞状态转换和基板的物理区隔的机制尚不清楚。

附：英文原文

Title: Mechanical forces across compartments coordinate cell shape and fate transitions to generate tissue architecture

Author: Villeneuve, Clmentine, Hashmi, Ali, Ylivinkka, Irene, Lawson-Keister, Elizabeth, Miroshnikova, Yekaterina A., Prez-Gonzlez, Carlos, Myllymki, Satu-Marja, Bertillot, Fabien, Yadav, Bhagwan, Zhang, Tao, Matic Vignjevic, Danijela, Mikkola, Marja L., Manning, M. Lisa, Wickstrm, Sara A.

Issue&Volume: 2024-02-01

Abstract: Morphogenesis and cell state transitions must be coordinated in time and space to produce a functional tissue. An excellent paradigm to understand the coupling of these processes is mammalian hair follicle development, which is initiated by the formation of an epithelial invagination—termed placode—that coincides with the emergence of a designated hair follicle stem cell population. The mechanisms directing the deformation of the epithelium, cell state transitions and physical compartmentalization of the placode are unknown. Here we identify a key role for coordinated mechanical forces stemming from contractile, proliferative and proteolytic activities across the epithelial and mesenchymal compartments in generating the placode structure. A ring of fibroblast cells gradually wraps around the placode cells to generate centripetal contractile forces, which, in collaboration with polarized epithelial myosin activity, promote elongation and local tissue thickening. These mechanical stresses further enhance compartmentalization of Sox9 expression to promote stem cell positioning. Subsequently, proteolytic remodelling locally softens the basement membrane to facilitate a release of pressure on the placode, enabling localized cell divisions, tissue fluidification and epithelial invagination into the underlying mesenchyme. Together, our experiments and modelling identify dynamic cell shape transformations and tissue-scale mechanical cooperation as key factors for orchestrating organ formation.

DOI: 10.1038/s41556-023-01332-4

Source: https://www.nature.com/articles/s41556-023-01332-4