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肌的表达和收缩功能因干细胞衍生的心肌细胞的重复发生变化而改变.

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脱离和重叠人类干细胞衍生的心肌细胞 (hESC-CMs和hiPSC-CMs) 改变了它们的髓重链 (MyHC) 表达和功能. 机械感知和基因表达的这些变化是可逆的,并且对于体外测试很重要.

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科学领域:

  • 心血管生物学 心血管生物学
  • 干细胞生物学 干细胞生物学
  • 细胞力学 细胞力学

背景情况:

  • 人体腹腔心肌细胞 (CMs) 主要表达β-肌酸重链 (β-MyHC) 异型,对收缩功能至关重要.
  • 人类胚胎干细胞衍生心肌细胞 (hESC-CMs) 通常在特定基质上长期培养后表达β-MyHC.
  • 机械操纵对心肌细胞表型的影响尚未完全理解.

研究的目的:

  • 调查脱离和重置hESC-CMs如何影响它们的细胞功能和肌肉素重链 (MyHC) 异形表达.
  • 评估这些变化的可逆性,并确定潜在的分子机制.
  • 为了评估人类诱导的多能干细胞衍生CMs (hiPSC-CMs) 的类似效应.

主要方法:

  • 长期培养的hESC-CMs被酶分离并重新涂层.
  • 微机械测试用于测量与力相关的动力参数.
  • 单细胞免疫光分析了MyHC异型表达 (β-MyHC和α-MyHC).
  • RNA测序和基因丰富分析确定了受影响的途径.
  • 研究了焦点粘附激酶 (FAK) 的作用.

主要成果:

  • 替代引发了与力相关的动力学和过渡的显著变化,类似于α-MyHC肌纤维.
  • 在hESC-CMs中,α-MyHC表达迅速上调,在hESC-CMs和hiPSC-CMs中异质性增加.
  • 这些功能和分子变化在两周内是可逆的.
  • 基因丰富分析突出了机械感知/转导通路的变化,包括整蛋白信号和FAK.

结论:

  • 脱离和重叠会大大改变基因表达,MyHC组成和干细胞衍生的CMs的功能.
  • 机械感知和机械传导通路受到这些过程的显著影响.
  • 必须考虑这些诱导的变化,以便准确地解释使用干细胞衍生的CMs的下游体外试验.