Thoroughly describing all cells, tissues and structures of the developing human heart over time is crucial for understanding congenital heart defects. However, important intervals of human heart development, such as the late embryonic and early fetal period at the end of the first trimester, were under-represented. To overcome this gap in knowledge, Stéphane Zaffran, Heather Etchevers and colleagues provide single-nucleus RNA sequencing and spatial transcriptomic data from fetal human hearts between 8.4 and 10.7 post-conception weeks, and integrate these data with existing datasets of earlier human embryonic heart development. Through this comprehensive approach, the authors identify previously unreported cell types and states, such as subpopulations of cycling cardiomyocytes and anatomically distinct populations of stromal cells, as well as a transient cardiomyofibroblast progenitor. The authors support their transcriptomic data using validatory imaging, including RNAscope and immunofluorescence staining of heart sections. Finally, using whole-mount light-sheet imaging, the researchers present 3D arrangements of cardiac blood vessels, nerves and valves in samples from the third gestational month. Together, these data provide an atlas of unparalleled spatial and temporal resolution for the characterisation of human-specific aspects of early heart development.
