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

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-ce...

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Bibliographic Details
Published in:	Nature communications Vol. 15; no. 1; p. 3064
Main Authors:	Kumar, Naveen, Prakash, Pon Ganish, Wentland, Christian, Kurian, Shilpa Mary, Jethva, Gaurav, Brinkmann, Volker, Mollenkopf, Hans-Joachim, Krammer, Tobias, Toussaint, Christophe, Saliba, Antoine-Emmanuel, Biebl, Matthias, Jürgensen, Christian, Wiedenmann, Bertram, Meyer, Thomas F., Gurumurthy, Rajendra Kumar, Chumduri, Cindrilla
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 09-04-2024 Nature Publishing Group Nature Portfolio
Subjects:	13 13/100 13/105 13/106 14 14/1 14/105 14/19 14/32 14/63 38 38/91 631/136/2060 631/532/2139 631/553/1833 631/67/1504/1477 96 Animals Carcinogenesis Carcinogens Cell interactions Crosstalk Embryogenesis Epidermal growth factor Epidermal Growth Factor - metabolism Epithelial cells Epithelium Esophagogastric Junction - metabolism Esophagus Fibroblast growth factors Fibroblasts Fibroblasts - metabolism Gastrointestinal diseases Heterogeneity Humanities and Social Sciences Metaplasia Mice Molecular modelling multidisciplinary Organoids Science Science (multidisciplinary) Signal transduction Single-Cell Analysis Spatial analysis Stomach Transcriptomics Transforming Growth Factor beta - metabolism Transforming growth factor-b Wnt protein
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Summary:	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. Elucidating the gastroesophageal junction’s development is key to comprehending its disease susceptibility. Here, the authors mapped its development, uncovering cellular diversity and interaction dynamics using advanced spatiotemporal single-cell analysis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-47173-z