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| Status |
Public on Apr 04, 2022 |
| Title |
LGR5 expressing skin fibroblasts define a major hub perturbed in Systemic Sclerosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systemic sclerosis (SSc) is an incurable autoimmune disease with high morbidity and mortality rates, with no effective treatment. Here, we conducted a population scale single-cell genomic analysis of skin and blood samples of 56 healthy controls, and 97 SSc patients at different stages of disease. We found immune compartment activation in only a subset of diffuse SSc patients, but global dysregulation of the stromal compartment, including a novel subset of LGR5+ scleroderma associated fibroblasts (ScAF). ScAF cells are mainly localized in the deep reticular dermis of healthy subjects and are dramatically perturbed morphologically and molecularly in SSc patients. Single-cell multiome profiling of the epigenetic and transcriptional landscapes of stromal cells in healthy subjects and SSc patients, revealed ScAF-specific markers, pathways, and transcription factors important in disease development. Systematic analysis combining the clinical metadata and molecular features of the patients, associates specific ScAF targets with disease pathogenesis and SSc clinical traits. Our study provides a high-resolution atlas of the entire spectrum of sclerodermatous skin, proposing a paradigm shift in the understanding of SSc disease and facilitating the development of new biomarkers and therapeutic strategies for SSc.
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| Overall design |
Patients who were diagnosed with SSc based on the 2013 American College of Rheumatology/European League against Rheumatism revised criteria for SSc (Van Den Hoogen et al., 2013), were recruited to the study from rheumatology departments in two medical centers in Israel. We excluded SSc patients under biological Disease-Modifying antirheumatic Drugs (DMARDs). After informed consent (in accordance with Helsinki declaration), skin samples were obtained through punch biopsy (4 mm), 10 cm distal to the elbow and placed in saline containing tubes on ice and then transferred to cold FACS buffer (EDTA pH8.0 2mM, BSA 0.5% in PBS). Whole blood samples were collected at the time of skin biopsy, were placed in EDTA-containing tubes (Beckton Dickenson) on ice and diluted 1:1 with ice cold FACS buffer. Skin and blood samples immediately transported to the lab. As a control, we also collected blood and skin samples from healthy patients following the same procedure.
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| Web link |
https://doi.org/10.1016/j.cell.2022.03.011
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| Contributor(s) |
Gur C, Wang S, Amit I |
| Citation(s) |
35381199 |
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| Submission date |
Jan 26, 2022 |
| Last update date |
Jul 04, 2022 |
| Contact name |
Ido Amit |
| E-mail(s) |
ido.amit@weizmann.ac.il
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| Phone |
972-8-9343338
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| Organization name |
Weizmann Institute of Science
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| Department |
Immunology
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| Street address |
234 Herzl st.
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| City |
Rehovot |
| ZIP/Postal code |
760001 |
| Country |
Israel |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (727)
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| Relations |
| BioProject |
PRJNA800731 |
| SRA |
SRP356854 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE195452_Cell_metadata_v26_anno.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
| GSE195452_RAW.tar |
795.8 Mb |
(http)(custom) |
TAR (of TAR, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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