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Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function.
- Ainsworth, Richard I (author)
- Hammaker, Deepa (author)
- Nygaard, Gyrid (author)
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- Ansalone, Cecilia (author)
- Machado, Camilla (author)
- Zhang, Kai (author)
- Zheng, Lina (author)
- Carrillo, Lucy (author)
- Wildberg, Andre (author)
- Kuhs, Amanda (author)
- Boyle, David L (author)
- Firestein, Gary S (author)
- Wang, Wei (author)
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- (creator_code:org_t)
- 2022-10-20
- 2022
- English.
- In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted activepathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Humans
- Synoviocytes
- metabolism
- Transcription Factors
- genetics
- metabolism
- Systems Biology
- Transfer Factor
- metabolism
- Arthritis
- Rheumatoid
- metabolism
- Fibroblasts
- metabolism
- Cell Proliferation
- genetics
- Cell Line
- Transforming Growth Factor beta
- metabolism
- Cells
- Cultured
- Synovial Membrane
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Machado, Camilla
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- Zheng, Lina
- Carrillo, Lucy
- Wildberg, Andre
- Kuhs, Amanda
- Svensson, Mattia ...
- Boyle, David L
- Firestein, Gary ...
- Wang, Wei
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