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The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
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在不同的基质硬度下,E-cadherin负面调节hESCs内皮分化.

Fan Zhang1,2,3, Lu Zheng1,2, Yi Wu1,2

  • 1Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.

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概括

刚性基板通过减少E-cadherin表达来促进人类胚胎干细胞 (hESC) 分化成最终内皮 (DE). 阻断E-cadherin进一步增强DE分化,突出其在干细胞命运中的作用.

关键词:
最终的内皮分化.这是E-cadherin.胚胎干细胞是一种胚胎干细胞.基板的刚性 基板的刚性哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈哈

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科学领域:

  • 发育生物学 发展生物学
  • 干细胞生物学 干细胞生物学
  • 生物材料科学 生物材料科学

背景情况:

  • 由E-cadherin调解的细胞间粘附,对于胚胎干细胞 (ESC) 多能性和分化至关重要.
  • 细胞外机械微环境,包括基质刚性,影响干细胞的行为.
  • 了解这些相互作用对于控制再生医学的干细胞分化至关重要.

研究的目的:

  • 研究E-cadherin复合体和基质刚度对人类胚胎干细胞 (hESCs) 终极内皮 (DE) 差异化的影响.
  • 为了阐明分子机制连接E-cadherin,YAP信号和差异化标记在响应机械线索.

主要方法:

  • 使用一个体外模型,培养hESCs (H1细胞) 在不同硬度的聚烯胺水凝上.
  • 量化E-cadherin表达,细胞分化成DE,以及YAP局部化.
  • 实验阻止了E-cadherin的功能,以评估其对分化和细胞粘附动态的影响.

主要成果:

  • 较硬的基板增加了hESCs分化为DE的比例.
  • 细胞间E-cadherin表达随着分化进展和基质刚度的增加而降低.
  • E-cadherin阻塞增强了DE分化,促进了细胞粘附分解,并诱导了YAP核转位,与GATA6和CXCR4表达以依赖于硬度的方式相关联.

结论:

  • 通过E-cadherin介导的细胞间粘附和基质刚性是DE指导的hESC分化的关键调节者.
  • 减少E-cadherin表达和YAP核转位是促进硬基质分化的关键事件.
  • 这项研究提供了通过调节细胞矩阵相互作用和细胞对细胞粘附来控制hESC命运的见解.