4.5 Article

Laminin promotes differentiation of rat embryonic stem cells into cardiomyocytes by activating the integrin/FAK/PI3K p85 pathway

Journal

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 23, Issue 5, Pages 3629-3640

Publisher

WILEY
DOI: 10.1111/jcmm.14264

Keywords

cardiomyocyte differentiation; FAK; integrin; laminin; PI3K; rat embryonic stem cell

Funding

  1. National Natural Science Foundation of China [81670208, 81870242]
  2. Shanghai Committee of Science and Technology [16140904200, 18JC1414300]
  3. Fundamental Research Fund for the Central Universities
  4. Fund for Subject Pi lot Program of Tongji University
  5. Key Laboratory of Regenerative Biology of Chinese Academy of Science

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The generation of germline competent rat embryonic stem cells (rESCs) allows the study of their lineage commitment. Here, we developed a highly efficient system for rESC-derived cardiomyocytes, and even the formation of three-dimensional (3D)-like cell clusters with cTNT and alpha-Actinin. We have validated that laminin can interact with membrane integrin to promote the phosphorylation of both phosphatidylinositol 3-kinase (PI3K) p85 and the focal adhesion kinase (FAK). In parallel, GATA4 was up-regulated. Upon inhibiting the integrin, laminin loses the effect on cardiomyocyte differentiation, accompanied with a down-regulation of phosphorylation level of PI3K p85 and FAK. Meanwhile, the expression of Gata4 was inhibited as well. Taken together, laminin is a crucial component in the differentiation of rESCs into cardiomyocytes through increasing their proliferation via interacting with integrin pathway. These results provide new insights into the pathways mediated by extracellular laminin involved in the fate of rESC-derived cardiomyocytes.

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