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 and
Cindrilla Chumduri ()
Additional contact information
Naveen Kumar: Aarhus University
Pon Ganish Prakash: University of Würzburg
Christian Wentland: University of Würzburg
Shilpa Mary Kurian: University of Würzburg
Gaurav Jethva: University of Würzburg
Volker Brinkmann: Max Planck Institute for Infection Biology
Hans-Joachim Mollenkopf: Max Planck Institute for Infection Biology
Tobias Krammer: Helmholtz-Center for Infection Research (HZI)
Christophe Toussaint: Helmholtz-Center for Infection Research (HZI)
Antoine-Emmanuel Saliba: Helmholtz-Center for Infection Research (HZI)
Matthias Biebl: Charité University Medicine
Christian Jürgensen: Charité University Medicine
Bertram Wiedenmann: Charité University Medicine
Thomas F. Meyer: Max Planck Institute for Infection Biology
Rajendra Kumar Gurumurthy: University of Würzburg
Cindrilla Chumduri: Aarhus University
Nature Communications, 2024, vol. 15, issue 1, 1-20
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.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47173-z
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DOI: 10.1038/s41467-024-47173-z
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