Reduced Cell-ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation.
Reduced Cell-ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation.
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作者：
细胞-细胞外基质（ECM）相互作用的机械调节对于决定多能干细胞分化至关重要。然而，并非所有的多能细胞均质地响应，这导致异质细胞群。当细胞，如小鼠上胚层干细胞（EpiSC），在集群中培养，分化过程中的异质性效应甚至更加明显。虽然过去的研究暗示信号通路的变化是异质性的根本原因，但分化的生物物理学方面尚未得到充分考虑。在这里，我们证明了EpiSC分化的异质性源于殖民地大小的差异以及集落内细胞与ECM之间不同程度的相互作用。共聚焦成像表明，殖民地周边的细胞与表面建立了良好的接触，而殖民地中心的细胞与表面平均分离1-2 µm。EpiSC集落内细胞的牵引力测量显示，外周细胞产生大的牵引力，而殖民地中心细胞不产生。EpiSC集落的有限元建模显示，由殖民地外围的细胞产生的牵引力抬离殖民地中心，防止殖民地中心经历分化。总之，我们的研究结果表明异质EpiSC集落分化的生物物理调节。
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect during differentiation is even more pronounced. While past studies implicated variations in signaling pathways to be the root cause of heterogeneity, the biophysical aspects of differentiation have not been thoroughly considered. Here, we demonstrate that the heterogeneity of EpiSC differentiation arises from differences in the colony size and varying degrees of interactions between cells within the colonies and the ECM. Confocal imaging demonstrates that cells in the colony periphery established good contact with the surface while the cells in the colony center were separated by an average of 1–2 µm from the surface. Traction force measurements of the cells within the EpiSC colonies show that peripheral cells generate large tractions while the colony center cells do not. A finite element modeling of EpiSC colonies shows that tractions generated by the cells at the colony periphery lift off the colony center preventing the colony center from undergoing differentiation. Together, our results demonstrate a biophysical regulation of heterogeneous EpiSC colony differentiation.
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影响因子：
5.9
作者：
Guo G;von Meyenn F;Santos F;Chen Y;Reik W;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
4.3
作者：
Hayashi Y;Furue MK
通讯作者：
Furue MK
影响因子：
3.7
作者：
Chowdhury F;Li Y;Poh YC;Yokohama-Tamaki T;Wang N;Tanaka TS
通讯作者：
Tanaka TS
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
3.4
作者：
Engler, A;Bacakova, L;Discher, D
通讯作者：
Discher, D