| Summary: | Summary: The heart is the central organ of the circulatory system, and its proper development is vital for maintaining human life. Here, we used single-cell RNA sequencing to profile the gene expression landscapes of ∼4,000 cardiac cells from human embryos and identified four major types of cells: cardiomyocytes (CMs), cardiac fibroblasts, endothelial cells (ECs), and valvar interstitial cells (VICs). Atrial and ventricular CMs acquired distinct features early in heart development. Furthermore, both CMs and fibroblasts show stepwise changes in gene expression. As development proceeds, VICs may be involved in the remodeling phase, and ECs display location-specific characteristics. Finally, we compared gene expression profiles between humans and mice and identified a series of unique features of human heart development. Our study lays the groundwork for elucidating the mechanisms of in vivo human cardiac development and provides potential clues to understand cardiac regeneration. : Cui et al. reveal the transcriptional landscapes of human fetal heart development at single-cell resolution and identify critical biological features of different cell types, providing insights into the molecular mechanisms of human heart development. Keywords: human fetal heart development, single-cell RNA-seq, cardiomyocytes, cardiac fibroblasts, endothelial cells, valvar interstitial cells, extracellular matrix, cross-species comparison, single-cell transcriptome analysis, human embryonic development
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