On June 7,2023, HE Ximiao 's research group, Professor of Tongji Medical College, Huazhong University of Science and Technology, published a research paper entitled " A Distinct Mononuclear Cardiac Diploid Subpopulation with Minimal Cell-Cell Communications Persist in Embryonic and Adult Mammalian Heart " online in Frontiers of Medicine.

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4⁺Tnni1⁺MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

This work is supported by the national key research and development plan and the independent innovation plan of Huazhong University of Science and Technology. Frontiers of Medicine is sponsored by Higher Education Press and Chinese Academy of Engineering. It is published by Springer, Germany. The Chinese Academy of Sciences is divided into medical area 1 TOP. It is the academic journal with the highest impact factor in China 's comprehensive medical journals (the latest impact factor is 9.93 ). Dr. ZHU Miaomiao and Associate Professor LIANG Huamin of the Department of Physiology were the co-first authors, and Professor HE Ximiao was the corresponding author.

Paper link：https://journal.hep.com.cn/fmd/EN/10.1007/s11684-023-0987-9