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| Status |
Public on Jan 16, 2024 |
| Title |
Molecular reframing of fibroblasts during resolution of arthritis [scRNA] |
| Organism |
Mus musculus |
| 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.
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| Overall design |
Cells from synovial joints were separated by fluorescence-activated cell sorting from R5 x R26tdTomato mice in either healthy, serum transfer arthritis (STA), or STA treated with Il23mc condition. R5-fatemap ILCs (viable CD45+ tdTomato+ CD3- TCRb- TCRgd- CD11b- GR-1-) and fibroblasts (viable CD45- GR-1-) were sorted from each animal and analyzed using scRNAseq. Libraries were generated from pooled animals, each of them individually separated by antibody hashes directed against CD45 and B2m.
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| Contributor(s) |
Rauber S, Mohammadian H, Angeli M, Yang K, 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-Nürnberg
|
| Department |
Department of Medicine 3 - Rheumatology and Immunology
|
| Street address |
Ulmenweg 18
|
| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (12)
|
| GSM7146910 |
Synovial ILCs, R5 healthy mice gene expression library |
| GSM7146911 |
Synovial ILCs, R5 healthy mice HTO library |
| GSM7146912 |
Synovial ILCs, R5 STA mice gene expression library |
| GSM7146913 |
Synovial ILCs, R5 STA mice HTO library |
| GSM7146914 |
Synovial ILCs, R5 STA + IL23 mice gene expression library |
| GSM7146915 |
Synovial ILCs, R5 STA + IL23 mice HTO library |
| GSM7146916 |
Synovial Fibroblasts, R5 healthy/STA/STA+Il23 mice gene expression library |
| GSM7146917 |
Synovial Fibroblasts, R5 healthy/STA/STA+Il23 mice HTO library |
| GSM7146918 |
Synovial ILCs, R5 healthy/STA mice gene expression library |
| GSM7146919 |
Synovial ILCs, R5 healthy/STA mice HTO library |
| GSM7146920 |
Synovial Fibs, R5 healthy/STA mice gene expression library |
| GSM7146921 |
Synovial Fibs, R5 healthy/STA mice HTO library |
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| This SubSeries is part of SuperSeries: |
| GSE228982 |
Molecular reframing of fibroblasts during resolution of arthritis |
|
| Relations |
| BioProject |
PRJNA952267 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228980_R5_ILCs_fibroblasts_filterted_merged_metadata.txt.gz |
498.7 Kb |
(ftp)(http) |
TXT |
| GSE228980_R5_STA_r1_Fibroblasts_barcodes.tsv.gz |
32.9 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_Fibroblasts_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_Fibroblasts_matrix.mtx.gz |
60.8 Mb |
(ftp)(http) |
MTX |
| GSE228980_R5_STA_r1_ILCs_HC_barcodes.tsv.gz |
13.9 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_HC_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_HC_matrix.mtx.gz |
14.0 Mb |
(ftp)(http) |
MTX |
| GSE228980_R5_STA_r1_ILCs_STA_Il23mc_barcodes.tsv.gz |
19.8 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_STA_Il23mc_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_STA_Il23mc_matrix.mtx.gz |
19.5 Mb |
(ftp)(http) |
MTX |
| GSE228980_R5_STA_r1_ILCs_STA_barcodes.tsv.gz |
11.5 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_STA_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r1_ILCs_STA_matrix.mtx.gz |
11.8 Mb |
(ftp)(http) |
MTX |
| GSE228980_R5_STA_r2_Fibroblasts_barcodes.tsv.gz |
22.3 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r2_Fibroblasts_features.tsv.gz |
284.2 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r2_Fibroblasts_matrix.mtx.gz |
40.9 Mb |
(ftp)(http) |
MTX |
| GSE228980_R5_STA_r2_ILCs_barcodes.tsv.gz |
38.4 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r2_ILCs_features.tsv.gz |
284.2 Kb |
(ftp)(http) |
TSV |
| GSE228980_R5_STA_r2_ILCs_matrix.mtx.gz |
41.7 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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