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Cyclic stretching induces maturation of human induced pluripotent stem cell-derived cardiomyocytes through nuclear mechanotransduction
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  • Yongjun Jang,
  • Myeongjin Song,
  • Seung-Jong Kim,
  • Yongdoo Park
Yongjun Jang
Korea University
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Myeongjin Song
Korea University
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Seung-Jong Kim
Korea University
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Yongdoo Park
Korea University

Corresponding Author:[email protected]

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Abstract

During cardiogenesis, cardiac cells receive various stimuli, such as biomechanical and chemical cues, from the surrounding microenvironment, and these signals induce the maturation of heart cells. Mechanical force, especially tensile force in the heart, is one of the key stimuli that induce cardiomyocyte (CM) maturation through mechanotransduction, a process through which physical cues are transformed into biological responses. However, the effects and mechanisms of tensile force on cell maturation are poorly studied. In this study, we developed a cyclic stretch system that mimics the mechanical environment of the heart by loading tensile force to human induced pluripotent stem cell (hiPSC)-derived CMs. HiPSC-CMs cultured with the cyclic stretch system showed increased cell alignment, sarcomere length and expression of maturation markers in mRNA, such as TNNI3, MYL2 and TTN, compared to static cultures. Especially, the expression of genes related to nuclear mechanotransduction, such as Yap1, lamin A/C, plectin (PLEC), and desmin (DES), was increased in the cyclically stretched hiPSC-CMs. Furthermore, the volume of the nucleus was increased by as much as 120% in the cyclic stretch group. These results revealed that nuclear mechanotransduction induced by tensile force is involved in CM maturation. Together, these findings provide novel evidence suggesting that nuclear mechanotransduction induced by tensile force is involved in the regulation of cardiac maturation.