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

被引:21
作者
Caetano, Ana J. [1 ,7 ]
Redhead, Yushi [1 ]
Karim, Farah [1 ,2 ]
Dhami, Pawan [3 ]
Kannambath, Shichina [3 ]
Nuamah, Rosamond [3 ]
Volponi, Ana A. [1 ]
Nibali, Luigi [4 ]
Booth, Veronica [4 ]
D'Agostino, Eleanor M. [5 ]
Sharpe, Paul T. [1 ,6 ]
Zhuan, Bian
机构
[1] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Craniofacial & Regenerat Biol, London, England
[2] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Dept Endodont, London, England
[3] Kings Coll London, Guys Hosp, Guys & St Thomas NHS Fdn Trust, NIHR BRC Genom Res Platform,Sch Med, London, England
[4] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Dept Periodontol, London, England
[5] Colworth Sci Pk, Unilever R&D, Sharnbrook, England
[6] Inst Anim Physiol & Genet, Lab Odontogenesis & Osteogenesis, Brno, Czech Republic
[7] Queen Mary Univ London, Ctr Oral Immunobiol & Regenerat Med, Barts & London Sch Med & Dent, London, England
来源
ELIFE | 2023年 / 12卷
基金
英国生物技术与生命科学研究理事会;
关键词
gingiva; fibroblast; inflammation; oral mucosa; spatial genomics; periodontal disease; Human; CHEMOKINES; BROWSER; CELLS;
D O I
10.7554/eLife.81525
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:22
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