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Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10

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 h...

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Autores principales: Caetano, Ana J, Redhead, Yushi, Karim, Farah, Dhami, Pawan, Kannambath, Shichina, Nuamah, Rosamond, Volponi, Ana A, Nibali, Luigi, Booth, Veronica, D'Agostino, Eleanor M, Sharpe, Paul T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897724/
https://www.ncbi.nlm.nih.gov/pubmed/36648332
http://dx.doi.org/10.7554/eLife.81525
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author Caetano, Ana J
Redhead, Yushi
Karim, Farah
Dhami, Pawan
Kannambath, Shichina
Nuamah, Rosamond
Volponi, Ana A
Nibali, Luigi
Booth, Veronica
D'Agostino, Eleanor M
Sharpe, Paul T
author_facet Caetano, Ana J
Redhead, Yushi
Karim, Farah
Dhami, Pawan
Kannambath, Shichina
Nuamah, Rosamond
Volponi, Ana A
Nibali, Luigi
Booth, Veronica
D'Agostino, Eleanor M
Sharpe, Paul T
author_sort Caetano, Ana J
collection PubMed
description 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.
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spelling pubmed-98977242023-02-04 Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10 Caetano, Ana J Redhead, Yushi Karim, Farah Dhami, Pawan Kannambath, Shichina Nuamah, Rosamond Volponi, Ana A Nibali, Luigi Booth, Veronica D'Agostino, Eleanor M Sharpe, Paul T eLife Cell Biology 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. eLife Sciences Publications, Ltd 2023-01-17 /pmc/articles/PMC9897724/ /pubmed/36648332 http://dx.doi.org/10.7554/eLife.81525 Text en © 2023, Caetano et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Caetano, Ana J
Redhead, Yushi
Karim, Farah
Dhami, Pawan
Kannambath, Shichina
Nuamah, Rosamond
Volponi, Ana A
Nibali, Luigi
Booth, Veronica
D'Agostino, Eleanor M
Sharpe, Paul T
Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title_full Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title_fullStr Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title_full_unstemmed Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title_short Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10
title_sort spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through cxcl8 and cxcl10
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897724/
https://www.ncbi.nlm.nih.gov/pubmed/36648332
http://dx.doi.org/10.7554/eLife.81525
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