Elucidating cardiomyocyte heterogeneity and maturation dynamics through integrated single-cell and spatial transcriptomics

The intricate development and functionality of the mammalian heart are influenced by the heterogeneous nature of cardiomyocytes (CMs). In this study, single-cell and spatial transcriptomics were utilized to analyze cells from neonatal mouse hearts, resulting in a comprehensive atlas delineating the transcriptional profiles of distinct CM subsets. A continuum of maturation states was elucidated, emphasizing a progressive developmental trajectory rather than discrete stages. This approach enabled the mapping of these states across various cardiac regions, illuminating the spatial organization of CM development and the influence of the cellular microenvironment. Notably, a subset of transitional CMs was identified, characterized by a transcriptional signature marking a pivotal maturation phase, presenting a promising target for therapeutic strategies aimed at enhancing cardiac regeneration. This atlas not only elucidates fundamental aspects of cardiac development but also serves as a valuable resource for advancing research into cardiac physiology and pathology, with significant implications for regenerative medicine.