First Author | Kumar N | Year | 2024 |
Journal | Nat Commun | Volume | 15 |
Issue | 1 | Pages | 3064 |
PubMed ID | 38594232 | Mgi Jnum | J:347128 |
Mgi Id | MGI:7620774 | Doi | 10.1038/s41467-024-47173-z |
Citation | Kumar N, et al. (2024) Decoding spatiotemporal transcriptional dynamics and epithelial fibroblast crosstalk during gastroesophageal junction development through single cell analysis. Nat Commun 15(1):3064 |
abstractText | 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-beta, FGF, EGF, and PDGF. Our results suggest that fibroblasts predominantly send FGF and TGF-beta 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. |