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Series GSE228953 Query DataSets for GSE228953
Status Public on Jan 16, 2024
Title Molecular reframing of fibroblasts during resolution of arthritis [RNA]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
Overall design Total RNA was isolated from arthroscopic synovial biopsies of patients with rheumatoid arthritis (RA; N=10) and psoriatic arthritis (PsA; N=8) and bulk RNA sequencing was performed.
Contributor(s) Rauber S, Mohammdian H, Hanlon M, Fearon U, Veale D, Ramming A
Citation(s) 38396288
Submission date Apr 04, 2023
Last update date Mar 12, 2024
Contact name Hashem Mohammadian
Organization name University of Erlangen-N├╝rnberg
Department Department of Medicine 3 - Rheumatology and Immunology
Street address Ulmenweg 18
City Erlangen
ZIP/Postal code 91054
Country Germany
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM7146146 Synovia of PsA patient ST2
GSM7146147 Synovia of PsA patient ST3
GSM7146149 Synovia of PsA patient ST4
This SubSeries is part of SuperSeries:
GSE228982 Molecular reframing of fibroblasts during resolution of arthritis
BioProject PRJNA952240

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Supplementary file Size Download File type/resource
GSE228953_RAW.tar 50.1 Mb (http)(custom) TAR (of TAR)
GSE228953_clinical_metadata.txt.gz 193 b (ftp)(http) TXT
GSE228953_normalized_counts.txt.gz 2.2 Mb (ftp)(http) TXT
GSE228953_raw_counts.txt.gz 766.5 Kb (ftp)(http) TXT
GSE228953_rlog_trnasformed_counts.txt.gz 3.3 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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