Single-cell analysis of Barrett's esophagus and carcinoma reveals cell types conferring risk via genetic predisposition.

Inherited genetic variants contribute to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but it is unknown which cell types are involved in this process. We performed single-cell RNA sequencing of BE, EAC, and paired normal tissues and integrated genome-wide association data to determine cell-type-specific genetic risk and cellular processes that contribute to BE and EAC. The analysis reveals that EAC development is driven to a greater extent by local cellular processes than BE development and suggests that one cell type of BE origin (intestinal metaplasia cells) and cellular processes that control the differentiation of columnar cells are of particular relevance for EAC development. Specific subtypes of fibroblasts and endothelial cells likely contribute to BE and EAC development, while dendritic cells and CD4⁺ memory T cells seem to contribute to BE development. The diagnostic value of markers characterizing the cell types and cellular processes should be explored for EAC prediction.