Collagen/β(1) integrin interaction is required for embryoid body formation during cardiogenesis from murine induced pluripotent stem cells.
Collagen/β(1) integrin interaction is required for embryoid body formation during cardiogenesis from murine induced pluripotent stem cells.
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DOI：
10.1186/1471-2121-14-5
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发表时间：
2013-01-25
期刊：
影响因子：
--
通讯作者：
Zheng QS
中科院分区：
文献类型：
--
作者：
Zeng D;Ou DB;Wei T;Ding L;Liu XT;Hu XL;Li X;Zheng QS
整合素介导的干细胞与细胞外基质（ECM）之间的相互作用在决定干细胞命运的过程中起着重要作用。然而，ECM/整合素相互作用在小鼠诱导多能干细胞（miPSC）心脏发生期间胚状体（EB）形成中的作用仍不清楚。在本研究中，I型胶原和β1整合素在miPSC衍生的EB形成期间协同表达和上调，在分化的第3天达到峰值表达。β1整合素阻断抗体阻断胶原/β1整合素相互作用导致产生缺陷型EB，其特征在于尺寸减小和缺乏由原始内胚层细胞组成的壳样层。自发搏动活动、心脏特异性基因表达和心肌肌钙蛋白T（cTnT）免疫染色的定量显示，这些缺陷型miPSC衍生的EB的心脏分化低于对照EB。这些发现表明胶原/β1整联蛋白相互作用是miPSC衍生的EB的生长和心脏分化所需的，并且将有助于EB内基质微环境的未来工程化，以有效地指导多能干细胞的心脏命运，从而促进心血管再生。
The interactions between stem cells and extracellular matrix (ECM) mediated by integrins play important roles in the processes that determine stem cell fate. However, the role of ECM/integrin interaction in the formation of embryoid bodies (EBs) during cardiogenesis from murine induced pluripotent stem cells (miPSCs) remains unclear. In the present study, collagen type I and β1 integrin were expressed and upregulated synergistically during the formation of miPSC-derived EBs, with a peak expression at day 3 of differentiation. The blockage of collagen/β1 integrin interaction by β1 integrin blocking antibody resulted in the production of defective EBs that were characterized by decreased size and the absence of a shell-like layer composed of primitive endoderm cells. The quantification of spontaneous beating activity, cardiac-specific gene expression and cardiac troponin T (cTnT) immunostaining showed that the cardiac differentiation of these defective miPSC-derived EBs was lower than that of control EBs. These findings indicate that collagen/β1 integrin interaction is required for the growth and cardiac differentiation of miPSC-derived EBs and will be helpful in future engineering of the matrix microenvironment within EBs to efficiently direct the cardiac fate of pluripotent stem cells to promote cardiovascular regeneration.
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作者：
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