{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Theodoros Simakou"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-15203"],"description":["Synovial resident macrophages in humans play a key role in maintaining tissue and synovial fluid homeostasis and typically exhibit protective phenotypes. However, at the start of rheumatoid arthritis, macrophages can adopt inflammation-permissive phenotypes. The factors that influence macrophage phenotype during the early stages of arthritis are not yet fully understood. Interestingly, in mice, mechanical stress is required for the localization of joint inflammation. Given the critical roles of macrophages, we investigated whether mechanosensation contributes to the regulation of macrophage phenotypes. PIEZO1, a well-established mechanosensor expressed on macrophages, regulates various macrophage functions, including migration and phagocytosis. We found that PIEZO1 activation in macrophages shifted their phenotype to a tissue-resident (MERTKhigh, CD36high), inflammation-permissive phenocopy (TREM2low, VSIG4low), with elevated MHC class II and cytokine secretion. Additionally, in vivo activation of PIEZO1 in mice produced similar effects in synovial tissue macrophages (STMs) and led to increased recruitment of monocytes and neutrophils. By dissecting the PIEZO1 signalling pathway, we were able to restore the protective macrophage phenotype by inhibiting calpain signalling and knocking-out HIF1α, both downstream mediators of PIEZO1 activation. Furthermore, we observed that PIEZO1 expression is present in synovial macrophages from patients with active rheumatoid arthritis and decreases during remission, suggesting a link between macrophage PIEZO1 expression and disease activity"],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - RNA was extracted using RNeasy Microkit, following manufacture's instructions (Qiagen, 74004).","Sequencing - Libraries were sequenced using Illumina by University of Glasgow, MVLS Shared Research Facility.","Sample Collection - On the days of the extraction, the cells were washed with D-PBS in the 24 well plate. Then the cells were lysed using RLT buffer + 1% b-mercaptoethanol, at RT, mixing well.","Growth Protocol - PIEZO1 activation using Yoda1  Macrophages were differentiated from CD14 monocytes (from 6 healthy donors) as described for 6 days in complete RPMI supplemented with 20 ng/mL M-CSF, changing medium on day 3. On day 5 of differentiation, the cells were stimulated with 20 uM Yoda1, for 12 hours (overnight), before being lysed for RNA extraction.","Library Construction - Libraries were prepared by University of Glasgow, MVLS Shared Research Facility, for Illumina sequencing."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - The data was also processed by the MVLS Shared Research Facility. In brief, the fastq files were quality control checked using FastQC (Andrews, GitHub), reads were then trimmed using FastP, and then aligned to the human reference genome (Ensembl, release 112) using HISAT2. Read counts were generated using featureCounts. The normalised expression and differential expression values were generated using DESeq2 (Love, Huber, and Anders 2014), with default settings and no additional covariates."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["NextSeq 500"],"study_type":["RNA-seq of coding RNA"],"species":["Homo sapiens"],"pubmed_authors":["Theodoros Simakou"],"additional_accession":[]},"is_claimable":false,"name":"PIEZO1 activation and signalling is associated with inflammation permissive phenocopy of synovial resident macrophages in early arthritis","description":"Synovial resident macrophages in humans play a key role in maintaining tissue and synovial fluid homeostasis and typically exhibit protective phenotypes. However, at the start of rheumatoid arthritis, macrophages can adopt inflammation-permissive phenotypes. The factors that influence macrophage phenotype during the early stages of arthritis are not yet fully understood. Interestingly, in mice, mechanical stress is required for the localization of joint inflammation. Given the critical roles of macrophages, we investigated whether mechanosensation contributes to the regulation of macrophage phenotypes. PIEZO1, a well-established mechanosensor expressed on macrophages, regulates various macrophage functions, including migration and phagocytosis. We found that PIEZO1 activation in macrophages shifted their phenotype to a tissue-resident (MERTKhigh, CD36high), inflammation-permissive phenocopy (TREM2low, VSIG4low), with elevated MHC class II and cytokine secretion. Additionally, in vivo activation of PIEZO1 in mice produced similar effects in synovial tissue macrophages (STMs) and led to increased recruitment of monocytes and neutrophils. By dissecting the PIEZO1 signalling pathway, we were able to restore the protective macrophage phenotype by inhibiting calpain signalling and knocking-out HIF1α, both downstream mediators of PIEZO1 activation. Furthermore, we observed that PIEZO1 expression is present in synovial macrophages from patients with active rheumatoid arthritis and decreases during remission, suggesting a link between macrophage PIEZO1 expression and disease activity","dates":{"release":"2026-01-31T00:00:00Z","modification":"2026-01-31T02:02:03.6Z","creation":"2025-06-05T09:16:47.546Z"},"accession":"E-MTAB-15203","cross_references":{"ENA":["ERP173184"],"EFO":["EFO_0002944","EFO_0004170","EFO_0003789","EFO_0005518","EFO_0003816","EFO_0003738","EFO_0004184"]}}