Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
- King's College London, United Kingdom
- Unilever, United Kingdom
Abstract
The interplay among different cells in a tissue is essential for maintaining homeostasis. Although, disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided
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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory DiseaseNCBI Gene Expression Omnibus, GSE206621.
Article and author information
Author details
Funding
BBSRC (BB/P504506/1)
- Ana J Caetano
NIHR Biomedical Research Centre Guy's and St Thomas' NHS Foundation Trust and King's College London
- Paul T Sharpe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bian Zhuan, Wuhan University, China
Version history
- Received: June 30, 2022
- Preprint posted: July 5, 2022 (view preprint)
- Accepted: January 16, 2023
- Accepted Manuscript published: January 17, 2023 (version 1)
- Version of Record published: February 3, 2023 (version 2)
Copyright
© 2023, Caetano et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
eLife 12:e81525.
https://doi.org/10.7554/eLife.81525
Further reading
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