当前位置: X-MOL 学术Dev. Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Mechanical Tension Promotes Formation of Gastrulation-like Nodes and Patterns Mesoderm Specification in Human Embryonic Stem Cells
Developmental Cell ( IF 10.7 ) Pub Date : 2020-11-17 , DOI: 10.1016/j.devcel.2020.10.015
Jonathon M Muncie 1 , Nadia M E Ayad 1 , Johnathon N Lakins 2 , Xufeng Xue 3 , Jianping Fu 4 , Valerie M Weaver 5
Affiliation  

Embryogenesis is directed by morphogens that induce differentiation within a defined tissue geometry. Tissue organization is mediated by cell-cell and cell-extracellular matrix (ECM) adhesions and is modulated by cell tension and tissue-level forces. Whether cell tension regulates development by modifying morphogen signaling is less clear. Human embryonic stem cells (hESCs) exhibit an intrinsic capacity for self-organization, which motivates their use as a tractable model of early human embryogenesis. We engineered patterned substrates that recapitulate the biophysical properties of the early embryo and mediate the self-organization of “gastrulation-like” nodes in cultured hESCs. Tissue geometries that generated local nodes of high cell-adhesion tension directed the spatial patterning of the BMP4-dependent “gastrulation-like” phenotype by enhancing phosphorylation and junctional release of β-catenin to promote Wnt signaling and mesoderm specification. Furthermore, direct force application via mechanical stretching promoted BMP-dependent mesoderm specification, confirming that tissue-level forces can directly regulate cell fate specification in early human development.



中文翻译:

机械张力促进人胚胎干细胞中原肠胚形成样节点和中胚层规范的形成

胚胎发生是由形态发生素引导的,形态发生素在确定的组织几何形状内诱导分化。组织组织由细胞与细胞和细胞与细胞外基质(ECM)粘附介导,并受到细胞张力和组织水平力的调节。细胞张力是否通过改变形态发生素信号传导来调节发育尚不清楚。人类胚胎干细胞(hESC)表现出内在的自组织能力,这促使它们用作早期人类胚胎发生的易处理模型。我们设计了图案化的基质,可以概括早期胚胎的生物物理特性,并介导培养 hESC 中“原肠胚形成样”节点的自组织。产生高细胞粘附张力局部节点的组织几何形状通过增强β-连环蛋白的磷酸化和连接释放来促进 Wnt 信号传导和中胚层规范,从而指导 BMP4 依赖性“原肠胚形成样”表型的空间模式。此外,通过机械拉伸直接施加力促进了 BMP 依赖性中胚层规范,证实组织水平的力可以直接调节人类早期发育中的细胞命运规范。

更新日期:2020-12-21
down
wechat
bug