Ji Dong

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.

Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells' DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing.