|
| Status |
Public on Jan 01, 2017 |
| Title |
Gene expression in limited cutaneous systemic sclerosis skin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Systemic sclerosis (SSc) is an autoimmune disease characterized by clinical heterogeneity, multi-organ involvement, and complex genetic risk. Here, we report the first multi-tissue meta-analysis of ten independent SSc gene expression datasets. We identify a common immune-fibrotic expression axis across all tissues that is associated with the most severe disease phenotypes. The coexpression patterns conserved across tissues and phenotypes were used to query functional genomic networks, which allowed us to identify common and tissue-specific disease drivers. We find evidence of pro-fibrotic macrophages (MØs) in SSc end-target organs. Prominent genes in the skin functional genomic network are associated with SSc genetic risk and are modulated by immunosuppressive treatment in clinical improvers. These data suggest the interactions between T lymphocytes and MØs are a critical driver of disease and implicate MØs as central to SSc pathogenesis. In total, this study presents a mechanism for fibrosis in SSc end-target tissues, a set of putative therapeutic targets for modulating SSc, and a framework for multi-tissue functional genomic studies of complex human disease.
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| |
|
| Overall design |
Gene expression was measured in forearm skin punch biopsies in 24 limited cutaneous systemic sclerosis patients
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| |
|
| Contributor(s) |
Lafyatis R, Whitfield ML |
| Citation(s) |
28330499 |
| |
| Submission date |
Jan 12, 2016 |
| Last update date |
Jul 12, 2019 |
| Contact name |
Tammara Wood |
| E-mail(s) |
tammara.a.wood@dartmouth.edu
|
| Organization name |
Dartmouth Medical School
|
| Department |
Biomedical Data Science
|
| Lab |
Whitfield Lab
|
| Street address |
WTRB 674
|
| City |
Lebanon |
| State/province |
NH |
| ZIP/Postal code |
03756 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
|
| Samples (24)
|
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| This SubSeries is part of SuperSeries: |
| GSE76809 |
Multi-tissue functional genomic study of systemic sclerosis |
|
| Relations |
| BioProject |
PRJNA308611 |
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