Spatial dynamics of the developing human heart, part 2

To address spatial dynamics in the developing heart, we generated a comprehensive cardiac cell atlas by combining single cell and spatial transcriptomics approaches with validations using subcellular imaging-based transcriptomics. By analyzing almost 80 000 single cells and 70 000 spatially barcoded tissue regions from hearts collected between postconceptional weeks 5.5 and 14, we identified 11 coarse- and 72 fine-grained cell types and states, spatially linked them to structural components of the developing human heart, and predicted molecular interactions in finely resolved cellular niches of the fetal heart.

We provide novel insight into the specification of the pacemaker and conduction system and formation of cardiac valves and atrial septum, and decipher heterogeneity of the elusive cardiac fibroblast population. Furthermore, we present the early development of cardiac autonomic innervation and provide the first account of chromaffin cells in the human embryonic heart. In summary, our study delineates the cellular and molecular landscape of early human cardiogenesis, offering links between architecture of the developing heart to genetic causes of heart disease.