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J Cell Mol Med. 2019 May;23(5):3629-3640. doi: 10.1111/jcmm.14264. Epub 2019 Mar 25.

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

Wang D1,2,3, Wang Y1,2,3, Liu H1,2,3, Tong C2, Ying Q4, Sachinidis A5, Li L1,2,3, Peng L1,2,3.

Author information

1
Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
2
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
3
Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, China.
4
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
5
Institute of Neurophysiology and Center for Molecular Medicine, University of Cologne, Cologne, Germany.

Abstract

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 α-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.

KEYWORDS:

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

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