Nature Communications (Apr 2024)

Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis

  • Naveen Kumar,
  • Pon Ganish Prakash,
  • Christian Wentland,
  • Shilpa Mary Kurian,
  • Gaurav Jethva,
  • Volker Brinkmann,
  • Hans-Joachim Mollenkopf,
  • Tobias Krammer,
  • Christophe Toussaint,
  • Antoine-Emmanuel Saliba,
  • Matthias Biebl,
  • Christian Jürgensen,
  • Bertram Wiedenmann,
  • Thomas F. Meyer,
  • Rajendra Kumar Gurumurthy,
  • Cindrilla Chumduri

DOI
https://doi.org/10.1038/s41467-024-47173-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 20

Abstract

Read online

Abstract The gastroesophageal squamocolumnar junction (GE-SCJ) is a critical tissue interface between the esophagus and stomach, with significant relevance in the pathophysiology of gastrointestinal diseases. Despite this, the molecular mechanisms underlying GE-SCJ development remain unclear. Using single-cell transcriptomics, organoids, and spatial analysis, we examine the cellular heterogeneity and spatiotemporal dynamics of GE-SCJ development from embryonic to adult mice. We identify distinct transcriptional states and signaling pathways in the epithelial and mesenchymal compartments of the esophagus and stomach during development. Fibroblast-epithelial interactions are mediated by various signaling pathways, including WNT, BMP, TGF-β, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-β signals to the epithelia, while epithelial cells mainly send PDGF and EGF signals to fibroblasts. We observe differences in the ligands and receptors involved in cell-cell communication between the esophagus and stomach. Our findings provide insights into the molecular mechanisms underlying GE-SCJ development and fibroblast-epithelial crosstalk involved, paving the way to elucidate mechanisms during adaptive metaplasia development and carcinogenesis.