Paper - Review

DOI: 10.1126/science.abd1449

Abstract

1⃣ The origin of human metaplastic states 2⃣ their pronpensity
→ for cancer
→ is poorly understood

Barrett's esophagus
→ is a common metaplastic condition
← that increases the risk → for 1⃣ esophageal adenocarcinoma 2⃣ its cellular origin is enigmatic

Harvested tissues
← spanning the gastroesophageal juction
← from 1⃣ healthy 2⃣ diseased donors
← including isolation of esophageal sub-mucosal glands

A combination
← of 1⃣ single-cell transcriptomic profiliing 2⃣ in silico lineage tracing ← from methylation 3⃣ open chromatin 4⃣ somotic mutation analyses 5⃣ functional studies ← in organoid models
∴ Barrett's esophagus → originates from gastric cardia
→ through 1⃣ c-MYC 2⃣ HNF3A-driven transcriptional programs

Esophageal adenocarcinoma
→ arises ← from undifferentiated Barrett's esophagus cell types
← in the absence of a pathologically identifiable metaplastic precursor

---