Minimal contribution of IP3R2 in cardiac differentiation and derived ventricular-like myocytes from human embryonic stem cells

• Published in: Acta pharmacologica Sinica 2020-12, Vol.41 (12), p.1576-1586
• Main Authors: Zhang, Peng, Huang, Ji-jun, Ou-yang, Kun-fu, Liang, He, Li, Miao-ling, Wang, Yi-jie, Yang, Huang-tian
• Format: Article
• Language: English
• Subjects: Action potential; Biomedical and Life Sciences; Biomedicine; Calcium (intracellular); Calcium (reticular); Cardiomyocytes; Cell self-renewal; Cell therapy; Depolarization; Drug screening; Embryo cells; Endoplasmic reticulum; Heart; Immunology; Inositol 1,4,5-trisphosphate receptors; Internal Medicine; Medical Microbiology; Myocytes; Pharmacology/Toxicology; Phenylephrine; Progenitor cells; Stem cells; Vaccine; Ventricle
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/s41401-020-00528-w

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 the α 1 -adrenergic stimulation by phenylephrine (10 μmol/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.