{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Clarisse Ganier"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-17238"],"description":["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."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sequencing - Libraries were sequenced using an Illumina HiSeq 4000 device.","Library Construction - Immediately after flow cytometry, ~20,000 to 100,000 live single cells were loaded onto a Chromium chip and libraries were prepared through droplet encapsulation on the Chromium controller (10X Genomics; Pleasanton,  CA,  USA) using the Single Cell 3’ reagent kits following the manufacturer’s protocol. Library quantification was performed using the Qubit dsDNA HS Assay Kit (Life Technologies, Waltham, MA, USA), and cDNA integrity was assessed using D1000 ScreenTapes (Agilent Technologies).","Nucleic Acid Extraction - For library preparation, cells were thawed and resuspended in PBS with 2% FBS and DAPI (0.05mg/ml). Dead cells were removed through flow cytometry of the final cell suspension.","Sample Collection - Skin from HS surgery was kept in a cold environment immediately after resection and either directly processed for dissociation into cell suspensions or kept in MACS Tissue Storage Solution (Miltenyi Biotec, cat. no. 130-100-008) overnight. Large samples were cut into small pieces (0.5-1cm2) prior to further experimentation. Skin was enzymatically digested to separate epidermis from dermis with Dispase overnight at 4°C. The IFE was digested with a mixture of trypsin-EDTA and Versene for 15 minutes at 37oC. The dermis was dissociated following the Whole Skin Dissociation kit for human material (Miltenyi Biotec, cat. no. 130-101-540). Dermis samples were incubated with the enzyme solution for 3 hours in a shaking water bath at 37°C. Fetal bovine serum (FBS) was then added to the mix to terminate the process, and the cell suspensions were then filtered through 70-µm and 40µm cell strainers (Falcon). Cell suspensions were centrifuged at 1200rpm for 4 minutes at 4°C and supernatant was carefully aspirated. The collected cells were frozen in 10% DMSO in (FBS) and stored in liquid nitrogen tanks."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Standard Space Ranger output for 10x including gene matrices; barcodes etc"],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Bio-Rad CFX96 Real-time System","Epidermal cells : Trypsin dissociation / Dermal cells :MACS Whole Skin Dissociation Kit","BD LSRFortessa","Illumina HiSeq 4000","Advanced Sequencing Facility"],"study_type":["RNA-seq of coding RNA from single cells"],"species":["Homo sapiens"],"pubmed_authors":["Xinyi Du-Harpur","Clarisse Ganier"],"additional_accession":[]},"is_claimable":false,"name":"Pathogenic Keratinocyte States and Fibroblast Niches Define the Tissue Microenvironment in Severe Hidradenitis Suppurativa","description":"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.","dates":{"release":"2026-07-12T00:00:00Z","modification":"2026-07-12T01:00:50.906Z","creation":"2026-06-26T14:05:50.199Z"},"accession":"E-MTAB-17238","cross_references":{"ENA":["ERP195783"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005684","EFO_0005518","EFO_0003816","EFO_0004184"]}}