Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle

• DOI: 10.1038/s41467-021-25933-5
• Publication Date: 2021-10-01T11:02:54Z
• Authors: Xiuxiu Liu; Wenjuan Pu; Lingjuan He; Yan Li; Huan Zhao; Yi Li; Kuo Liu; Xiuzhen Huang; Wendong Weng; Qing-Dong Wang; Linghong Shen; Tao Zhong; Kun Sun; Reza Ardehali; Ben He; Bin Zhou
• Keywords: Male; 0301 basic medicine; 1.1 Normal biological development and functioning; Science; Cardiovascular; Regenerative Medicine; Fluorescence; Article; Mice; 03 medical and health sciences; Underpinning research; Genetics; 2.1 Biological and endogenous factors; Animals; Myocytes, Cardiac; Aetiology; Southern; Heart Disease - Coronary Heart Disease; Cell Proliferation; Microscopy; Myocytes; Blotting; Myocardium; Q; Cell Cycle; Heart; Flow Cytometry; Blotting, Southern; Heart Disease; Microscopy, Fluorescence; Female; Cardiac

AbstractCardiac regeneration involves the generation of new cardiomyocytes from cycling cardiomyocytes. Understanding cell-cycle activity of pre-existing cardiomyocytes provides valuable information to heart repair and regeneration. However, the anatomical locations and in situ dynamics of cycling cardiomyocytes remain unclear. Here we develop a genetic approach for a temporally seamless recording of cardiomyocyte-specific cell-cycle activity in vivo. We find that the majority of cycling cardiomyocytes are positioned in the subendocardial muscle of the left ventricle, especially in the papillary muscles. Clonal analysis revealed that a subset of cycling cardiomyocytes have undergone cell division. Myocardial infarction and cardiac pressure overload induce regional patterns of cycling cardiomyocytes. Mechanistically, cardiomyocyte cell cycle activity requires the Hippo pathway effector YAP. These genetic fate-mapping studies advance our basic understanding of cardiomyocyte cell cycle activity and generation in cardiac homeostasis, repair, and regeneration.