机构：[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
Type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) regulates the intracellular Ca2+ release from endoplasmic reticulum in human embryonic stem cells (hESCs), cardiovascular progenitor cells (CVPCs), and mammalian cardiomyocytes. However, the role of IP3R2 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 IP3R2 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 IP3R2 in the differentiation of hESCs to cardiomyocytes and in the hESC-derived cardiomyocytes. By using IP3R2 knockout (IP3R2KO) hESCs, we showed that IP3R2KO 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 the α1-adrenergic stimulation by phenylephrine (10 μmol/L), the amplitude and maximum rate of depolarization of action potential (AP) were slightly affected in the IP3R2KO hESC-derived cardiomyocytes at differentiation day 90, whereas the other parameters of APs and the Ca2+ transients did not show significant changes compared with these in the wide-type ones. These results demonstrate that IP3R2 has minimal contribution to the differentiation and function of human cardiomyocytes derived from hESCs, thus provide the new knowledge to the function of IP3R2 in the generation of human cardiac lineage cells and in the early cardiomyocytes.
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).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区医学
小类|1 区药学2 区化学综合
最新[2023]版：
大类|1 区医学
小类|1 区药学2 区化学：综合
第一作者：
第一作者机构：[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
通讯作者：
通讯机构：[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[5]Institute for Stem Cell and Regenerative, CAS, Beijing 100101, China
推荐引用方式(GB/T 7714)：
Peng Zhang,Ji-jun Huang,Kun-fu Ou-yang,et al.Minimal contribution of IP3R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells.[J].Acta Pharmacologica Sinica.2020,41(12):1576-1586.doi:10.1038/s41401-020-00528-w.
APA：
Peng Zhang,Ji-jun Huang,Kun-fu Ou-yang,He Liang,Miao-ling Li...&Huang-tian Yang.(2020).Minimal contribution of IP3R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells..Acta Pharmacologica Sinica,41,(12)
MLA：
Peng Zhang,et al."Minimal contribution of IP3R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells.".Acta Pharmacologica Sinica 41..12(2020):1576-1586
医学