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| Status |
Public on Jan 16, 2024 |
| Title |
Molecular reframing of fibroblasts during resolution of arthritis [scRNA 2] |
| 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 to isolate viable CD45- GR-1 cells or viable CD45- FAP+ Pdpn+ and processed for single-cell RNA sequencing using 10x Genomics Chromium Kits. Three libraries were generated for CD45- cells without enrichment for FAP+ Pdpn+ cells, each containing cells from four individual animals separated by antibody hashes directed against CD45 and B2m. Each of these three libraries contained a healthy wild-type reference (#4) and 3 arthritic hTNFtg197+ animals treated with Il23mc for 9 days (#1-3). Arthritic animals were either untreated or treated with TNF- or IL-17-inhibiting antibodies (one condition per library). An additional library was generated with viable CD45- FAP+ Pdpn+ cells containing five individually hashtag-tagged arthritic hTNFtg197+ animals treated with Il23mc for 9 days.
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| Contributor(s) |
Rauber S, Mohammadian H, Angeli M, Raimondo M, Labinsky H, 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) |
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| Samples (8)
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| GSM7146922 |
hTNFtg197 + Il23mc and wilde type healthy gene expression library |
| GSM7146923 |
hTNFtg197 + Il23mc and wilde type healthy HTO library |
| GSM7146924 |
hTNFtg197 + Il23mc + TNFi and wilde type gene expression library |
| GSM7146925 |
hTNFtg197 + Il23mc + TNFi and wilde type healthy HTO library |
| GSM7146926 |
hTNFtg197 + Il23mc + IL-17i and wilde type gene expression library |
| GSM7146927 |
hTNFtg197 + Il23mc + IL-17i and wilde type HTO library |
| GSM7146928 |
hTNFtg197 + Il23mc Fap+ synovial cells gene expression library |
| GSM7146929 |
hTNFtg197 + Il23mc Fap+ synovial cells HTO library |
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| This SubSeries is part of SuperSeries: |
| GSE228982 |
Molecular reframing of fibroblasts during resolution of arthritis |
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| Relations |
| BioProject |
PRJNA952270 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE228981_FapPos_GSE228981_hTNFtg_Il23mc_barcodes.tsv.gz |
58.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_FapPos_GSE228981_hTNFtg_Il23mc_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_FapPos_GSE228981_hTNFtg_Il23mc_matrix.mtx.gz |
115.6 Mb |
(ftp)(http) |
MTX |
| GSE228981_hTNFtg-Il23mc_fibroblasts_merged_metadata.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE228981_hTNFtg_Il23mc_IL-17i_barcodes.tsv.gz |
63.8 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_IL-17i_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_IL-17i_matrix.mtx.gz |
131.7 Mb |
(ftp)(http) |
MTX |
| GSE228981_hTNFtg_Il23mc_TNFi_barcodes.tsv.gz |
53.6 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_TNFi_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_TNFi_matrix.mtx.gz |
105.2 Mb |
(ftp)(http) |
MTX |
| GSE228981_hTNFtg_Il23mc_barcodes.tsv.gz |
58.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_features.tsv.gz |
284.1 Kb |
(ftp)(http) |
TSV |
| GSE228981_hTNFtg_Il23mc_matrix.mtx.gz |
113.1 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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