134: Single-cell view of Barrett's esophagus and EAC

Wenzel M et al., Cell Genomics - This episode reviews a single-cell transcriptional atlas comparing Barrett's esophagus, intestinal metaplasia, normal esophagus/gastric samples and esophageal adenocarcinoma. The study uses single-cell RNA profiling and UMAP clustering to resolve epithelial, stromal and immune cell populations, identify gastric-like and intestinal metaplasia cell states, and characterize tumor-associated CNV and transcriptional programs. We unpack the cell-type maps, marker gene patterns and implications for understanding progression from Barrett's lesions to EAC. Key terms: Barrett's esophagus, esophageal adenocarcinoma, intestinal metaplasia, single-cell RNA-seq, cell atlas.

Study Highlights:
The authors performed single-cell RNA‑seq with UMAP clustering across samples from Barrett's esophagus, intestinal metaplasia, gastric and esophageal adenocarcinoma specimens to define cell states. They identified discrete epithelial clusters (foveolar cells, chief cells, parietal cells, intestinal metaplasia cells, enteroendocrine cells) and multiple EAC tumor clusters, and reported CNV-level differences and transcriptional signatures distinguishing EAC from non-malignant tissues. The atlas documents gastric-like cell states within Barrett's lesions and changes in stromal and immune compartments associated with progression.

Conclusion:
Single-cell profiling maps cellular diversity across Barrett's esophagus, intestinal metaplasia and esophageal adenocarcinoma, producing an atlas to dissect tissue-specific and tumor-associated transcriptional programs.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Single-cell analysis of Barrett’s esophagus and carcinoma reveals cell types conferring risk via genetic predisposition

First author:
Wenzel M

Journal:
Cell Genomics

DOI:
10.1016/j.xgen.2025.100980

Reference:
Wenzel M.C., Dasmeh P., Plum P.S., Giel A., Hoppe S., Franitza M., et al.. Single-cell analysis of Barrett’s esophagus and carcinoma reveals cell types conferring risk via genetic predisposition. Cell Genomics, 5, 100980. (2025). 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/

Support:
Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00

Official website https://basebybase.com

On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/single-cell-maps-link-intestinal-metaplasia-to-esophageal-adenocarcinoma-risk

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-09-11.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited core scientific themes: Barrett's esophagus and cancer risk, single-cell RNA sequencing atlas, LDSR integration with GWAS, intestinal metaplasia as a risk-rich cell type, distinct EAC tumor clusters, microenvironment contributions, and translational/clinical implications.
- transcript topics: Barrett's esophagus and esophageal adenocarcinoma risk; Single-cell RNA sequencing atlas across BE, intestinal metaplasia, normal esophagus, gastric tissue, and EAC; LDSR integration of GWAS risk variants with cell-type expression; Intestinal metaplasia cells as key risk-enriched population; Esophageal cancer tumor clusters (EAC-01 to EAC-04) with distinct programs; Tumor microenvironment and stromal/immune enrichment of risk

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Single-cell atlas generated across Barrett's esophagus, intestinal metaplasia, normal esophagus, and gastric tissues with esophageal adenocarcinoma (EAC) samples using single-cell
- GWAS-derived cancer risk variants overlaid with single-cell map via linkage disequilibrium score regression (LDSR) to identify cell-type enrichment
- Intestinal metaplasia cells show the strongest enrichment for esophageal cancer risk variants, despite relative genomic stability
- EAC contains multiple tumor clusters with divergent transcriptional programs (e.g., EAC-02 proliferative via WNT11 and CNV patterns; EAC-01 invasive via MMP/MMP7-related activity)
- Microenvironmental cell types (fibroblasts, memory CD4+ T cells, plasmacytoid dendritic cells) also show risk variant enrichment
- Barrett's esophagus risk is described as more systemic/mechanical (reflux mechanics, LES integrity) whereas cancer risk is driven by local cellular processes

QC result: Pass.