Multi-tissue functional genomic study of systemic sclerosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tammara Wood
PROVIDER: E-GEOD-76809 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic gene expression subsets. Gene expression measured in skin from mice with sclerodermatous graft-versus-host disease, bleomycin-induced fibrosis, or Tsk1/+ and Tsk2/+ mice was mapped to human orthologs and compared to SSc skin biopsy-derived gene expression.
2015-08-13 | E-GEOD-71991 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic gene expression subsets. Gene expression measured in skin from mice with sclerodermatous graft-versus-host disease, bleomycin-induced fibrosis, or Tsk1/+ and Tsk2/+ mice was mapped to human orthologs and compared to SSc skin biopsy-derived gene expression.
2015-08-13 | E-GEOD-71995 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-13 | E-GEOD-71999 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic gene expression subsets. Gene expression measured in skin from mice with sclerodermatous graft-versus-host disease, bleomycin-induced fibrosis, or Tsk1/+ and Tsk2/+ mice was mapped to human orthologs and compared to SSc skin biopsy-derived gene expression.
2015-08-13 | E-GEOD-71998 | biostudies-arrayexpress
Project description:To assess the safety, efficacy, and molecular change associated with treatment of patients with early, diffuse cutaneous systemic sclerosis (dcSSc) with nilotinib (Tasigna™). In this open-label pilot trial 6 adult patients with early dcSSc received nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score (MRSS) after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray.
2015-08-27 | E-GEOD-65405 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) is a polygenic, autoimmune disorder of unknown etiology, characterized by the excessive accumulation of extracellular matrix (ECM) proteins, vascular alterations, and autoantibodies. The tight skin (Tsk)2/+ mouse model of SSc demonstrates signs similar to SSc including tight skin and excessive deposition of dermal ECM proteins. By linkage analysis, we mapped the Tsk2 gene mutation to less than 3 megabases on chromosome 1. We performed both RNA sequencing of skin transcripts and genome capture DNA sequencing of the region spanning this interval in Tsk2/+ and wild-type littermates. A missense point mutation in the procollagen III amino terminal propeptide segment (PIIINP) of Col3a1 was found to be the best candidate for Tsk2, so both in vivo and in vitro genetic complementation tests were used to prove that this Col3a1 mutation is the Tsk2 gene. All previously documented mutations in the human Col3a1 gene are associated with Ehlers-Danlos syndrome, a connective tissue disorder that leads to a defect in type III collagen synthesis. The Tsk2 point mutation is the first documented gain-of-function mutation associated with Col3a1, which leads instead to fibrosis. This discovery provides insight into the mechanism of skin fibrosis manifested by Tsk2/+ mice. For the transfection experiment, three Col3a1 knockout fibroblast transfected with WT Col3a1 samples and three Col3a1 knockout fibroblast transfected with Tsk2 Col3a1 samples were used. For the 4-week female, three WT mice and three Tsk2 total skin RNA were used.
2015-09-24 | E-GEOD-61728 | biostudies-arrayexpress
Project description:Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. The EMS epidemic in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopathological and immunogenetic features of a new case of L-tryptophan-associated EMS along with evidence of activated transforming growth factor-ß and interleukin-4 signaling in the lesional skin. 6 samples were analyzed to include EMS patient and two replicates along with three normal controls
2012-01-28 | E-GEOD-26934 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series Attached to this SuperSeries page is a data matrix of all 359 samples included in this SuperSeries. The values are given as Log(base2) of R/G Lowess Normalized Ratio (Mean) representing reference/test.
2016-01-14 | E-GEOD-76886 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-25 | E-GEOD-59787 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) shows complex clinical manifestations including progressive skin and internal organ fibrosis. SSc can be divided into 'intrinsic subsets' by gene expression suggesting patient-specific heterogeneity in pathogenesis or temporal evolution of disease. Here we validate these subsets using an independent patient population, and test whether the genes vary over time with patients changing subsets as disease progresses, or if the genes are a stable feature of the patients within each subset. Skin biopsies were analyzed from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient 'intrinsic subsets' described previously with gene expression associated with cell proliferation, inflammatory processes, and a normal-like group. Serial skin biopsies showed consistent and non-progressing gene expression. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset regardless of treatment regimen or the time point at which they were taken. This demonstrates the intrinsic subsets are an inherent, reproducible and stable feature of SSc that is independent of disease duration. Skin biopsies were analyzed from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls.
2012-03-23 | E-GEOD-32413 | biostudies-arrayexpress