# Single-cell atlas of human cardiac differentiation prioritizes 610 congenital heart disease variants

- Published: 2026-11-05 23:04 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: congenital heart disease, noncoding variants, single-cell multiomics, chromatin states, H3K27me3, H3K27ac, ETS1, vascular smooth muscle cells, cardiac differentiation, CRISPR knockin
- URL: https://realtech.media/news/rt-8ea27d3affb07c211129c604_single_cell_atlas/

**In a model of human cardiac differentiation, a variant near ETS1 shifted cells toward vascular smooth muscle fate, the authors report. The atlas sorts regulatory elements into six chromatin states.**

![Single-cell atlas of human cardiac differentiation prioritizes 610 congenital heart disease variants](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/b4dff85b3830ef8e.jpg)
*Evgeny Pelevin, Wikimedia Commons, CC BY 4.0*

Researchers reported in Science Advances a single-cell multiomic atlas of human cardiac differentiation. It was built by jointly profiling H3K27ac, H3K27me3, H3K4me3 and transcriptomes in individual cells [1]. The authors used it to classify cis-regulatory elements into six chromatin states [1].

This allowed them to prioritize 610 noncoding variants associated with congenital heart disease (CHD). The variants are enriched in lineage- and state-specific regulatory elements, including repressive and bivalent regions [1].

The team introduced selected variants by CRISPR knockin. According to the study, this perturbed the expression of nearby genes and impaired cardiac differentiation [1].

One Polycomb-marked variant near ETS1 (ETS proto-oncogene 1) was examined in detail. It caused local loss of H3K27me3, gain of H3K27ac and up-regulation of ETS1 [1]. At early stages, differentiation was redirected toward second-heart-field progenitors with epithelial characteristics. Ultimately it produced highly migratory ETS1-positive vascular smooth muscle cells [1].

The authors describe the work as a single-cell chromatin-state framework for interpreting noncoding CHD risk variants. They also report an ETS1-driven program linking Polycomb-deregulated noncoding variation to aberrant vascular smooth muscle fate commitment during human cardiogenesis [1].

## Sources

1. [Science Advances](https://doi.org/10.1126/sciadv.aeg4687)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-8ea27d3affb07c211129c604_single_cell_atlas/