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Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2018-Jan-01 , DOI: 10.1038/s41556-017-0005-z
Yekaterina A. Miroshnikova , Huy Q. Le , David Schneider , Torsten Thalheim , Matthias Rübsam , Nadine Bremicker , Julien Polleux , Nadine Kamprad , Marco Tarantola , Irène Wang , Martial Balland , Carien M. Niessen , Joerg Galle , Sara A. Wickström

To establish and maintain organ structure and function, tissues need to balance stem cell proliferation and differentiation rates and coordinate cell fate with position. By quantifying and modelling tissue stress and deformation in the mammalian epidermis, we find that this balance is coordinated through local mechanical forces generated by cell division and delamination. Proliferation within the basal stem/progenitor layer, which displays features of a jammed, solid-like state, leads to crowding, thereby locally distorting cell shape and stress distribution. The resulting decrease in cortical tension and increased cell-cell adhesion trigger differentiation and subsequent delamination, reinstating basal cell layer density. After delamination, cells establish a high-tension state as they increase myosin II activity and convert to E-cadherin-dominated adhesion, thereby reinforcing the boundary between basal and suprabasal layers. Our results uncover how biomechanical signalling integrates single-cell behaviours to couple proliferation, cell fate and positioning to generate a multilayered tissue.

中文翻译:

粘附力和皮层张力耦合细胞增殖和分化,以驱动表皮分层。

为了建立和维持器官的结构和功能,组织需要平衡干细胞的增殖和分化速率,并协调细胞命运与位置。通过量化和建模哺乳动物表皮中的组织应力和变形,我们发现这种平衡通过细胞分裂和分层产生的局部机械力来协调。基底茎/祖细胞层内的增殖表现出堵塞的固态状态,导致拥挤,从而局部扭曲细胞形状和应力分布。皮质张力的降低和细胞间粘附的增加触发了分化和随后的分层,从而恢复了基础细胞层的密度。分层后 当细胞增加肌球蛋白II活性并转化为E-钙黏着蛋白为主的粘附时,它们建立了高压状态,从而增强了基底层和基底上层之间的边界。我们的结果揭示了生物力学信号转导如何整合单细胞行为以耦合增殖,细胞命运和定位以产生多层组织。
更新日期:2017-12-11
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