Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Pathogenic Keratinocyte States and Fibroblast Niches Define the Tissue Microenvironment in Severe Hidradenitis Suppurativa - Visium

ABSTRACT: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful abscesses and tunnels in flexural sites. The mechanisms driving HS pathogenesis, particularly the interactions between epithelial, stromal and immune cell populations, remain incompletely understood. To characterise the cellular and molecular landscape of HS, we analyzed lesional skin from severe HS patients using single-cell RNA-sequencing and spatial transcriptomics, with a focus on fibroblast-keratinocyte interactions. We identified a migratory S100+ pathogenic keratinocyte state enriched within HS lesions and observed spatially distinct fibroblast populations associated with different tissue compartments. COL6A5+ papillary fibroblasts showed spatial association with undifferentiated keratinocyte populations and predicted fibroblast-keratinocyte communication networks, whereas APOD+ fibroblasts were associated with immune-rich regions containing activated B cells and plasma cells, consistent with TLO-like immune aggregates. Ligand-receptor inference and spatial analyses predicted extensive fibroblast-keratinocyte and fibroblast-immune interactions within HS lesions. These findings support a model in which severe HS contains distinct epithelial and inflammatory stromal niches that may contribute to disease persistence. More broadly, they provide a framework for understanding how epithelial, stromal and immune compartments interact within HS lesions and may help explain the limited efficacy of therapies targeting individual inflammatory pathways in the treatment of HS.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Clarisse Ganier

PROVIDER: E-MTAB-17297 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Background Hidradenitis suppurativa (HS), psoriasis (PsO) and atopic dermatitis (AD) are inflammatory skin diseases which, despite sharing some immunological pathways, have unique disease pathogenesis and distinct pathology. For example, Th17 cells are central to PsO pathogenesis and have also been implicated in HS inflammation. AD, on the other hand, is classically referred to as a Th2-mediated disease, however incidence of AD is twice as likely in HS patients compared with healthy individuals, demonstrating an association between HS and AD. Objective To date the transcriptomics of HS, PsO and AD have not been directly compared. Therefore this study aimed to evaluate the transcriptomic differences between HS, PsO and AD lesions to identify a biological signature that defines HS inflammation. Methods Bulk RNA sequencing was performed on 19 healthy controls, 15 HS, 21 PsO and 15 AD lesional skin samples. Results Principal component analysis (PCA) identified a distinct transcriptome in HS lesions compared with healthy control skin, with increased expression of inflammatory mediators and more active inflammatory pathways including TNF, IL-17 and B cell signalling pathways. PsO lesions were defined by a strong IL-17 signature and while an IL-17 signature existed in HS lesions, HS was distinguished from PsO lesions by a unique B cell signature. When compared to AD lesions, HS lesions had a more complex inflammatory profile involving TNF, B cell and NLR signalling while AD lesions had high expression of Th2-associated genes. Weighted gene co-expression analysis suggested T cell signalling and epidermal development are important characteristics of PsO lesions while HS lesions can be defined by complement activation, B cell signalling and fibroblast-associated pathways indicating the potential for scarring in HS. Cell type deconvolution identified an enrichment of keratinocytes and T cells in PsO, Th2 cells in AD and B cells and plasma cells in HS. Finally, gene expression analysis identified increased expression of B cell, plasma cell and immunoglobulin-associated genes in HS lesions relative to healthy control skin, PsO and AD lesions. Conclusion These data suggest that HS pathogenesis is more complex than AD or PsO and highlights an important role of B and plasma cells in HS inflammation.

Dataset Information

Pathogenic Keratinocyte States and Fibroblast Niches Define the Tissue Microenvironment in Severe Hidradenitis Suppurativa - Visium

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets