Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163199 | GEO | 2022/09/02
REPOSITORIES: GEO
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Project description:ObjectiveSystemic sclerosis (SSc) is characterized by widespread fibrosis and vascular complications. This study was undertaken to examine the chromatin landscape and transcription factor footprints in SSc, using an assay for genome-wide chromatin accessibility.MethodsDermal endothelial cells (ECs) and fibroblasts were isolated from healthy controls and patients with diffuse cutaneous SSc (dcSSc). Assay for transposase-accessible chromatin with sequencing (ATAC-seq) was performed to assess genome-wide chromatin accessibility at a read depth of ~150 million reads per sample. Transcription factor footprinting and motif binding analysis were performed, followed by functional experiments.ResultsChromatin accessibility was significantly reduced in dcSSc patients compared to healthy controls. Differentially accessible chromatin loci were enriched in pathways and gene ontologies involved in the nervous system, cell membrane projections and cilia motility, nuclear and steroid receptors, and nitric oxide. In addition, chromatin binding of transcription factors SNAI2, ETV2, and ELF1 was significantly increased in dcSSc ECs, while recruitment of RUNX1 and RUNX2 was enriched in dcSSc fibroblasts. We found significant down-regulation of the neuronal gene NRXN1 and up-regulation of SNAI2 and ETV2 in dcSSc ECs. In dcSSc fibroblasts, down-regulation of the neuronal gene ENTPD1 and up-regulation of RUNX2 were confirmed. Further functional analysis revealed that ETV2 and NRXN1 dysregulation affected angiogenesis in ECs, while ENTPD1 enhanced profibrotic properties in dcSSc fibroblasts.ConclusionOur data identify the chromatin blueprint of dcSSc, and suggest that neuronal-related characteristics of SSc ECs and fibroblasts could be a culprit for dysregulated angiogenesis and enhanced fibrosis. Targeting the key pathways and transcription factors identified might present novel therapeutic approaches in SSc.
| S-EPMC8324511 | biostudies-literature
Project description:We assessed transcriptomic changes in fibroblasts isolated from skin biopsies from diffuse cutaneous scleroderma patients before and after BET inhibitor JQ1 treatment
2022-03-01 | GSE186961 | GEO
Project description:RNA expression profiling was carried out for systemic sclerosis (scleroderma) on skin biopsies obtained from both diffuse scleroderma (dcSSc) and limited scleroderma (lcSSc) subjects patients and compared to normal subjects. The patient group comprised of 4 dcSSc and 2 lcSSc subjects, all of whom were Caucasian and belonged to the age range of 42-73 (Mean age = 61.6). Patient sample set consisted of 3 females and 3 males. Race matched female volunteers from the same geographical area were recruited as controls (n = 4) and belonged to the age range of 41-62 (Mean age = 52).
2015-03-25 | E-MEXP-1214 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE3886: Scleroderma Morphea Normal Fibroblasts GSE3887: Scleroderma Architecture Cell Lines Abstract: We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease Refer to individual Series
2006-03-07 | E-GEOD-4385 | biostudies-arrayexpress
Project description:Abstract: We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease This SuperSeries is composed of the SubSeries listed below.
2006-03-08 | GSE4385 | GEO
Project description:We have analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from 34 subjects: 17 patients with SSc with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea and 6 healthy controls. In total, 61 skin biopsies were analyzed. The addition of 14 technical replicates resulted in a total of 75 microarray hybridizations. The Intrinsic_scleroderma_genes.txt supplementary file lists the 995 genes with the most consistent expression between each forearm-back pair and technical replicates, but with the highest variance across all samples analyzed. An intrinsic gene identifier algorithm was used to select a set of intrinsic scleroderma genes. A total of 34 experimental groups were defined, each representing the 34 different subjects in our study. Replicate hybridizations for a given patient were assigned to the same experimental group. Each gene was analyzed and assigned a score that is inversely related to how intrinsic the gene's expression is across the samples analyzed. The analysis was repeated on randomized data in order to estimate a False Discovery Rate (FDR). An intrinsic score of 0.3 selected 995 genes with an FDR of 4% (39 ± 7 genes) while retaining reproducible clustering of technical replicates. Keywords: global gene expression profiling using Agilent Whole Human genome oligo arrays
2008-07-15 | GSE9285 | GEO
Project description:We have analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from 34 subjects: 17 patients with SSc with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea and 6 healthy controls. In total, 61 skin biopsies were analyzed. The addition of 14 technical replicates resulted in a total of 75 microarray hybridizations. The Intrinsic_scleroderma_genes.txt supplementary file lists the 995 genes with the most consistent expression between each forearm-back pair and technical replicates, but with the highest variance across all samples analyzed. An intrinsic gene identifier algorithm was used to select a set of intrinsic scleroderma genes. A total of 34 experimental groups were defined, each representing the 34 different subjects in our study. Replicate hybridizations for a given patient were assigned to the same experimental group. Each gene was analyzed and assigned a score that is inversely related to how intrinsic the gene's expression is across the samples analyzed. The analysis was repeated on randomized data in order to estimate a False Discovery Rate (FDR). An intrinsic score of 0.3 selected 995 genes with an FDR of 4% (39 ± 7 genes) while retaining reproducible clustering of technical replicates. Keywords: global gene expression profiling using Agilent Whole Human genome oligo arrays common reference design; we used Universal Human Reference RNA (Stratagene) as our reference for every array; For every hybridization sample RNA was always labeled with Cy3, and reference RNA was always labeled with Cy5; Microarray hybridizations were performed for 61 RNA samples from 34 subjects resulting 61 hybridizations. Fourteen replicate hybridizations were added, resulting in a total of 75 microarray hybridizations.
2010-05-26 | E-GEOD-9285 | biostudies-arrayexpress
Project description:Genome-wide reduction in chromatin accessibility and unique transcription factor footprints in endothelial cells and fibroblasts in scleroderma skin
| PRJNA685180 | ENA
Project description:Fibroblast were isolated from either back or forearm punch biopsies taken by Dr. Kari Connolly(UCSF) from either normal control patients, patients with a diagnosis of Systemic Sclerosis with Diffuse Scleroderma and patients with a diagnosis of morphea. Scleroderma fibroblast were grown to confluence, media was changed and the RNA prepared from the cells 48 hrs later (to avoid serum responsive genes). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. User Defined
2005-12-20 | E-GEOD-3886 | biostudies-arrayexpress
Project description:Fibroblast were isolated from either back or forearm punch biopsies taken by Dr. Kari Connolly(UCSF) from either normal control patients, patients with a diagnosis of Systemic Sclerosis with Diffuse Scleroderma and patients with a diagnosis of morphea. Scleroderma fibroblast were grown to confluence, media was changed and the RNA prepared from the cells 48 hrs later (to avoid serum responsive genes). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2005-12-21 | GSE3886 | GEO