Cellular and molecular atlas of the healthy adult human heart

The heart is a complex organ composed of several cell types, including cardiomyocytes, endothelial cells and fibroblasts for a respective proportion of 35%, 60% and <20% as previously reported in both human and murine hearts by Pinto and colleagues ⁽¹⁾. However, a recent study by Litviňuková and colleagues gave a more exhaustive atlas of the healthy adult human heart ⁽²⁾.
Using single-cell and single-nucleus RNA sequencing combined with multiplex single-molecule fluorescence in situ hybridisation, they quantified the cellular composition in six distinct cardiac regions from 14 healthy cardiac donors (7 males and 7 females) and characterised their transcriptional signatures together with their cell-to-cell interactions. They reported 11 major cell types with a different enrichment between atria and ventricles. Indeed, contrary to Pinto’s study ⁽¹⁾, cardiomyocytes were the largest population (30% in atrial versus 50% in ventricular tissues), followed by either fibroblasts or mural cells, and lastly endothelial and immune cells. One intriguing result is the higher percentage of ventricular cardiomyocytes in female versus male hearts (56% vs 47%), which could explain the sex differences observed in cardiovascular diseases.
Looking deeper in each cell type composition, the authors showed a strong cardiomyocyte heterogeneity, comprising five ventricular and five atrial populations with distinct transcriptional profiles, notably a small population of highly energetic cardiomyocytes. The vascular compartment was shown to include seventeen populations, notably 10 endothelial, four pericytes and three vascular smooth muscle cells. Seven populations of fibroblasts were reported with specialised gene programmes required for cardiac remodelling according to each cardiac region. Twenty-one types of immune cells were identified, such as tissue-resident and monocyte-derived macrophages: the tissue-specificity of the homeostatic transcriptional circuits were demonstrated by comparison with skeletal muscle and kidney, notably for the myeloid cells. Finally, six neuronal cell clusters and four adipocyte cell types were characterised.
To conclude, the study by Litviňuková and colleagues enriches our knowledge of the healthy human heart cell composition together with their transcriptional profiles, therefore opening a new avenue for the cell-specificity in the cardiac pathophysiology. Similar exhaustive study in the mouse heart would be an invaluable asset to validate the relevance of the murine models in cardiovascular diseases.