Single-cell multi-omic atlas of human dendritic cell differentiation links inherited disease risk to specific immune cell subsets

Dendritic cells (DCs) are a rare but functionally critical population of immune cells that coordinate both innate and adaptive immune responses. Their rarity in peripheral blood and the limited availability of high-quality genomic reference data have previously made it difficult to connect common genetic variants identified in genome-wide association studies (GWAS) of immune-mediated diseases to specific DC subsets or molecular mechanisms.

A preprint posted on bioRxiv addresses this gap with a single-cell multi-omic atlas that captures both chromatin accessibility (via ATAC-seq) and gene expression profiles across DC subsets as they differentiate from haematopoietic stem and progenitor cells (HSPCs). By inferring regulatory networks from these paired datasets, the authors map which transcription factors and open chromatin regions are active at each stage of DC differentiation.

Critically, the atlas is then integrated with GWAS summary statistics from multiple immune-mediated diseases, enabling the authors to propose which specific DC subsets and regulatory elements are most likely to mediate inherited susceptibility signals. The work is a substantial genomic resource contribution. The preprint has not yet been peer-reviewed. Researchers in immunogenomics, GWAS functional follow-up, and the genetics of autoimmune disease are the primary audience.