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

• Published in: Journal of the American Heart Association Vol. 12; no. 23; p. e028287
• Main Authors: Shen, Junwei, Ma, Linlin, Hu, Jing, Li, Yanfei
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 05-12-2023; Wiley
• Subjects: Animals; Animals, Newborn; cardiac cell atlas; cardiomyocyte heterogeneity; Cell Differentiation; Cells, Cultured; Mice; Myocytes, Cardiac; Original Research; single‐cell RNA sequencing; Sinoatrial Node; terminal cardiomyocyte; cardiomyocyte heterogeneity; terminal cardiomyocyte; cardiac cell atlas; single‐cell RNA sequencing
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.122.028287

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.
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.
This mouse cardiac cell atlas improves our understanding of cardiomyocyte heterogeneity and provides a valuable reference in response to varying physiological conditions and diseases.