An atlas of transcribed enhancers across helper T cell diversity for decoding human diseases

Transcribed enhancer maps can reveal nuclear interactions underpinning
each cell type and connect specific cell types to diseases. Using a 5′
single-cell RNA sequencing approach, we defined transcription start sites
of enhancer RNAs and other classes of coding and non-coding RNAs in human
CD4+ T cells, revealing cellular heterogeneity and differentiation
trajectories. Integration of these datasets with single-cell chromatin
profiles showed that active enhancers with bidirectional RNA transcription
are highly cell type–specific, and disease heritability is strongly
enriched in these enhancers. The resulting cell type–resolved multimodal
atlas of bidirectionally transcribed enhancers, which we linked with
promoters using fine-scale chromatin contact maps, enabled us to
systematically interpret genetic variants associated with a range of
immune-mediated diseases.