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

Authors :
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
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.92e5c859ad5a452d9912442eb093da20
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-47173-z