Multi-modal refinement of the human heart atlas during the first gestational trimester

Congenital heart defects are collectively frequent and represent a significant burden for human health. Understanding the developmental origins of such anomalies in the first and longest-lived vital organ is key to improving diagnoses, prognoses and therapies. However, although the atlas of human cardiac cells before birth continues to benefit from increased sampling, equivalencies across different investigators’ datasets or with animal models remain tenuous. We have determined the individual transcriptomes of nearly fifty thousand human heart cells from both male and female fetuses and enriched their initial identification with spatiotemporal positional information. Integrations across modalities and time points both internally and with earlier atlases have revealed the existence of previously unidentified, transient contractile, conductive and stromal cell types and their likely lineage relationships during the first trimester. Multiple technical approaches enabled analyses at varying levels of spatiotemporal resolution to validate differently sized cardiac subpopulations in new datasets. This resource advances knowledge about cell-autonomous states and the repertory of contextual influences exerted by and on the diverse lineages of the developing human heart.