Single‐Cell Atlas of Neonatal Mouse Hearts Reveals an Unexpected Cardiomyocyte

Abstract

Background Single‐cell RNA sequencing is widely used in cancer research and organ development because of its powerful ability to analyze cellular heterogeneity. However, its application in cardiomyocytes is dissatisfactory mainly because the cardiomyocytes are too large and fragile to withstand traditional single‐cell approaches. Methods and Results Through designing the isolation procedure of neonatal mouse cardiac cells, we provide detailed cellular atlases of the heart at single‐cell resolution across 4 different stages after birth. We have obtained 10 000 cardiomyocytes; to our knowledge, this is the most extensive reference framework to date. Moreover, we have discovered unexpected erythrocyte‐like cardiomyocyte–terminal cardiomyocytes, comprising more than a third of all cardiomyocytes. Only a few genes are highly expressed in these cardiomyocytes. They are highly differentiated cardiomyocytes that function as contraction pumps. In addition, we have identified 2 cardiomyocyte‐like conducting cells, lending support to the theory that the sinoatrial node pacemaker cells are specialized cardiomyocytes. Notably, we provide an initial blueprint for comprehensive interactions between cardiomyocytes and other cardiac cells. Conclusions This mouse cardiac cell atlas improves our understanding of cardiomyocyte heterogeneity and provides a valuable reference in response to varying physiological conditions and diseases.