PDF(Pubmed)
Abstract：
Cell size is a crucial physical property that significantly impacts cellular physiology and function. However, the influence of cell size on stem cell specification remains largely unknown. Here, we investigated the dynamic changes in cell size during the differentiation of human pluripotent stem cells into definitive endoderm (DE). Interestingly, cell size exhibited a gradual decrease as DE differentiation progressed with higher stiffness. Furthermore, the application of hypertonic pressure or chemical to accelerate the reduction in cell size significantly and specifically enhanced DE differentiation. By functionally intervening in mechanosensitive elements, we have identified actomyosin activity as a crucial mediator of both DE differentiation and cell size reduction. Mechanistically, the reduction in cell size induces actomyosin-dependent angiomotin (AMOT) nuclear translocation, which suppresses Yes-associated protein (YAP) activity and thus facilitates DE differentiation. Together, our study has established a novel connection between cell size diminution and DE differentiation, which is mediated by AMOT nuclear translocation. Additionally, our findings suggest that the application of osmotic pressure can effectively promote human endodermal lineage differentiation.
摘要：
细胞大小是显著影响细胞生理学和功能的关键物理性质。然而,细胞大小对干细胞规格的影响在很大程度上仍然未知.这里,我们研究了人多能干细胞分化为定形内胚层(DE)过程中细胞大小的动态变化.有趣的是,随着DE分化的发展，细胞大小表现出逐渐减小的刚度较高。此外，应用高渗压力或化学物质来加速细胞大小的显著减小和特异性地增强DE分化。通过在功能上干预机械敏感元件，我们已经确定肌动球蛋白活性是DE分化和细胞大小减小的关键介质。机械上,细胞大小的减少诱导肌动球蛋白依赖性血管动蛋白（AMOT）核易位，抑制Yes相关蛋白（YAP）活性，从而促进DE分化。一起,我们的研究在细胞大小缩小和DE分化之间建立了一种新的联系，由AMOT核易位介导。此外,我们的发现表明，渗透压的应用可以有效地促进人的内胚层谱系分化。
