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http://dx.doi.org/10.14348/molcells.2022.0077

The Aurora Kinase Inhibitor CYC116 Promotes the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells  

Sijia, Ji (School of Life Science and Technology, ShanghaiTech University)
Wanzhi, Tu (School of Life Science and Technology, ShanghaiTech University)
Chenwen, Huang (State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences)
Ziyang, Chen (State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences)
Xinyue, Ren (State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences)
Bingqing, He (School of Life Science and Technology, ShanghaiTech University)
Xiaoyan, Ding (Stem Cell Bank/Stem Cell Core Facility, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences)
Yuelei, Chen (Stem Cell Bank/Stem Cell Core Facility, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences)
Xin, Xie (School of Life Science and Technology, ShanghaiTech University)
Publication Information
Molecules and Cells / v.45, no.12, 2022 , pp. 923-934 More about this Journal
Abstract
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have great potential in applications such as regenerative medicine, cardiac disease modeling, and in vitro drug evaluation. However, hPSC-CMs are immature, which limits their applications. During development, the maturation of CMs is accompanied by a decline in their proliferative capacity. This phenomenon suggests that regulating the cell cycle may facilitate the maturation of hPSC-CMs. Aurora kinases are essential kinases that regulate the cell cycle, the role of which is not well studied in hPSC-CM maturation. Here, we demonstrate that CYC116, an inhibitor of Aurora kinases, significantly promotes the maturation of CMs derived from both human embryonic stem cells (H1 and H9) and iPSCs (induced PSCs) (UC013), resulting in increased expression of genes related to cardiomyocyte function, better organization of the sarcomere, increased sarcomere length, increased number of mitochondria, and enhanced physiological function of the cells. In addition, a number of other Aurora kinase inhibitors have also been found to promote the maturation of hPSC-CMs. Our data suggest that blocking aurora kinase activity and regulating cell cycle progression may promote the maturation of hPSC-CMs.
Keywords
Aurora kinase inhibitor; cardiomyocyte differentiation; cell cycle; human pluripotent stem cell; maturation;
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