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

Science. 2024 Jul 5;385(6704):eadd8394. doi: 10.1126/science.add8394. Epub 2024 Jul 5.

Abstract

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 noncoding 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 that 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.

MeSH terms

  • Atlases as Topic
  • CD4-Positive T-Lymphocytes* / immunology
  • Cell Differentiation
  • Chromatin / genetics
  • Chromatin / metabolism
  • Enhancer Elements, Genetic*
  • Genetic Predisposition to Disease*
  • Humans
  • Promoter Regions, Genetic
  • Single-Cell Gene Expression Analysis
  • T-Lymphocytes, Helper-Inducer / immunology
  • Transcription Initiation Site*
  • Transcription, Genetic*

Substances

  • Chromatin