Minimal contribution of IP_(3)R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells  

作　　者：Peng Zhang Ji-jun Huang Kun-fu Ou-yang He Liang Miao-ling Li Yi-jie Wang Huang-tian Yang 

机构地区：[1]CAS Key Laboratory of Tissue Microenvironment and Tumor,Laboratory of Molecular Cardiology,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences(CAS)CAS,Shanghai 200031,China [2]Translational Medical Center for Stem Cell Therapy&Institute for Regenerative Medicine,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200123,China [3]School of Chemical Biology and Biotechnology,State Key Laboratory of Chemical Oncogenomics,Peking University Shenzhen Graduate School,Shenzhen 518055,China [4]Key Laboratory of Medical Electrophysiology of Ministry of Education,Medical Electrophysiology Key Lab of Sichuan province,Institute of Cardiovascular Research,Southwest Medical University,Luzhou 646000,China [5]Institute for Stem Cell and Regenerative,CAS,Beijing 100101,China

出　　处：《Acta Pharmacologica Sinica》2020年第12期1576-1586,共11页中国药理学报（英文版）

基　　金：This work was supported by grants from National Key R&D Program of China(2017YFA0103700 and 2016YFC1301204 to HTY);National Natural Science Foundation of China(81520108004,81470422 to HTY);the Strategic Priority Research Program of the CAS(No.XDA16010201 to HTY);Shanghai Natural Science Foundation(17ZR1435500 to JJH),and the Shenzhen Basic Research Foundation(KQJSCX20170330155020267).

摘　　要：Type 2 inositol 1,4,5-trisphosphate receptor(IP_(3)R2)regulates the intracellular Ca^(2+)release from endoplasmic reticulum in human embryonic stem cells(hESCs),cardiovascular progenitor cells(CVPCs),and mammalian cardiomyocytes.However,the role of IP_(3)R2 in human cardiac development is unknown and its function in mammalian cardiomyocytes is controversial.hESC-derived cardiomyocytes have unique merits in disease modeling,cell therapy,and drug screening.Therefore,understanding the role of IP_(3)R2 in the generation and function of human cardiomyocytes would be valuable for the application of hESC-derived cardiomyocytes.In the current study,we investigated the role of IP_(3)R2 in the differentiation of hESCs to cardiomyocytes and in the hESC-derived cardiomyocytes.By using IP_(3)R2 knockout(IP_(3)R2KO)hESCs,we showed that IP_(3)R2KO did not affect the self-renewal of hESCs as well as the differentiation ability of hESCs into CVPCs and cardiomyocytes.Furthermore,we demonstrated the ventricular-like myocyte characteristics of hESC-derived cardiomyocytes.Under theα1-adrenergic stimulation by phenylephrine(10μmol/L),the amplitude and maximum rate of depolarization of action potential(AP)were slightly affected in the IP_(3)R2KO hESC-derived cardiomyocytes at differentiation day 90,whereas the other parameters of APs and the Ca^(2+)transients did not show significant changes compared with these in the wide-type ones.These results demonstrate that IP_(3)R2 has minimal contribution to the differentiation and function of human cardiomyocytes derived from hESCs,thus provide the new knowledge to the function of IP_(3)R2 in the generation of human cardiac lineage cells and in the early cardiomyocytes.

关 键 词：IP_(3)R2 human embryonic stem cells differentiation cardiovascular progenitor cells CARDIOMYOCYTES function 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]