️ Episode 134: Single-Cell Maps Link Intestinal Metaplasia to Esophageal Adenocarcinoma Risk

In this episode of PaperCast Base by Base, we explore how single-cell RNA sequencing of Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC), and matched normal tissues reveals which cell types carry germline-linked risk and shape progression toward cancer.

Study Highlights:
The authors profiled epithelial, stromal, endothelial, and immune cells with 10x scRNA-seq and integrated genome-wide association data using partitioned heritability to map risk to specific cell types. They show that EAC development is driven more by local cellular programs than BE, with intestinal metaplasia cells—goblet cell–like cells expressing the intestinal stem cell marker OLFM4—emerging as pivotal in the transition toward malignancy. Tumor clusters displayed patient-specific copy-number profiles, and gene set analyses suggested that columnar cell differentiation programs, particularly within intestinal metaplasia, are closely tied to EAC risk. Fibroblast and endothelial subtypes also carried enriched risk signals, while plasmacytoid dendritic cells and memory CD4 T cells were linked to BE risk, highlighting immune involvement in the metaplastic stage.

Conclusion:
Linking GWAS risk loci to single-cell expression programs points to intestinal metaplasia and columnar differentiation states as key targets for early prediction and intervention in EAC.

Reference:
Wenzel MC, Dasmeh P, Plum PS, Giel A-S, Hoppe S, Franitza M, Jonas C, Thieme R, Zhao Y, Heider D, Palles C, Fitzgerald RC, Bruns CJ, Buettner R, Quaas A, Gockel I, Maj C, Chon S-H, Schumacher J, Hillmer AM. Single-cell analysis of Barrett’s esophagus and carcinoma reveals cell types conferring risk via genetic predisposition. Cell Genomics. 2025;5:100980. https://doi.org/10.1016/j.xgen.2025.100980

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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