Spatially resolved transcriptomics reveals pro-inflammatory fibroblast involved in lymphocyte recruitment through CXCL8 and CXCL10.
Ana J CaetanoYushi RedheadFarah KarimPawan DhamiShichina KannambathRosamond NuamahAna Angelova VolponiLuigi NibaliVeronica BoothEleanor M D'AgostinoPaul Thomas SharpePublished in: eLife (2023)
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.
Keyphrases
- single cell
- rna seq
- endothelial cells
- high throughput
- induced apoptosis
- public health
- high resolution
- healthcare
- mental health
- cell cycle arrest
- peripheral blood
- oxidative stress
- health information
- transcription factor
- electronic health record
- risk assessment
- cell death
- machine learning
- social media
- big data
- signaling pathway
- mass spectrometry
- quantum dots
- binding protein
- health promotion