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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease

View ORCID ProfileAna J. Caetano, Yushi Redhead, Farah Karim, Pawan Dhami, Shichina Kannambath, Rosamond Nuamah, Ana A. Volponi, Luigi Nibali, Veronica Booth, Eleanor M. D’Agostino, View ORCID ProfilePaul T. Sharpe
doi: https://doi.org/10.1101/2022.07.05.498778
Ana J. Caetano
1Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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  • ORCID record for Ana J. Caetano
Yushi Redhead
1Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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Farah Karim
1Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
2Department of Endodontics, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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Pawan Dhami
3NIHR BRC Genomics Research Platform, Guy’s and St Thomas’ NHS Foundation Trust, King’s College London School of Medicine, 10th Floor, Tower Wing, Guy’s Hospital, London, SE1 9RT
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Shichina Kannambath
3NIHR BRC Genomics Research Platform, Guy’s and St Thomas’ NHS Foundation Trust, King’s College London School of Medicine, 10th Floor, Tower Wing, Guy’s Hospital, London, SE1 9RT
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Rosamond Nuamah
3NIHR BRC Genomics Research Platform, Guy’s and St Thomas’ NHS Foundation Trust, King’s College London School of Medicine, 10th Floor, Tower Wing, Guy’s Hospital, London, SE1 9RT
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Ana A. Volponi
1Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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Luigi Nibali
4Department of Periodontology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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Veronica Booth
4Department of Periodontology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
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Eleanor M. D’Agostino
5Unilever R&D, Colworth Science Park, Sharnbrook, Bedfordshire, MK44 1LQ
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Paul T. Sharpe
1Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT
6Laboratory of Odontogenesis and Osteogenesis, Institute of Animal Physiology and Genetics, CAS, v.v.i., Veveri 97, 602 00 Brno, Czech Republic
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  • For correspondence: paul.sharpe@kcl.ac.uk
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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.

Competing Interest Statement

The authors have declared that no conflict of interest exists. However, E. DA is an employee of Unilever Plc.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 05, 2022.
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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease
Ana J. Caetano, Yushi Redhead, Farah Karim, Pawan Dhami, Shichina Kannambath, Rosamond Nuamah, Ana A. Volponi, Luigi Nibali, Veronica Booth, Eleanor M. D’Agostino, Paul T. Sharpe
bioRxiv 2022.07.05.498778; doi: https://doi.org/10.1101/2022.07.05.498778
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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease
Ana J. Caetano, Yushi Redhead, Farah Karim, Pawan Dhami, Shichina Kannambath, Rosamond Nuamah, Ana A. Volponi, Luigi Nibali, Veronica Booth, Eleanor M. D’Agostino, Paul T. Sharpe
bioRxiv 2022.07.05.498778; doi: https://doi.org/10.1101/2022.07.05.498778

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