ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Genome-Wide Reduction in Chromatin Accessibility and Unique Transcription Factor Footprints in Endothelial Cells and Fibroblasts in Scleroderma Skin.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.Annals of the rheumatic diseases · 2026Article
- Imbalance of Ciliary Programs Drives Fibroblast Differentiation and Fibrotic Signaling in Systemic Sclerosis.bioRxiv : the preprint server for biology · 2026Article
- Targeting Cardiac Fibroblast Plasticity for Antifibrotic and Regenerative Therapy in Heart Failure.Cells · 2026Review
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- Decoding vascular dysfunction in systemic sclerosis: from endothelial damage to clinical implications.Current opinion in rheumatology · 2025Review
- Multi-omic analysis reveals retinoic acid molecular drivers for dermal fibrosis and regenerative repair in the skin.Cell stem cell · 2025Article
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Targeting CD13/Aminopeptidase N as a Novel Therapeutic Approach for Scleroderma Fibrosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Recent Insights into Cellular and Molecular Mechanisms of Defective Angiogenesis in Systemic Sclerosis.Biomedicines · 2024Review
- Recent Insights into the Role of DNA Methylation and Histone Modifications in Systemic Sclerosis: A Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis.The Journal of investigative dermatology · 2023Article
- Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022Review
- Gut microbe-derived metabolite trimethylamine N-oxide activates PERK to drive fibrogenic mesenchymal differentiation.iScience · 2022Article
- Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development-New Insights From Technical Advances.Frontiers in cell and developmental biology · 2022Review
- Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis.Frontiers in immunology · 2022Article
- Contributions of Immune Cells and Stromal Cells to the Pathogenesis of Systemic Sclerosis: Recent Insights.Frontiers in pharmacology · 2022Review
- Advances in epigenetics in systemic sclerosis: molecular mechanisms and therapeutic potential.Nature reviews. Rheumatology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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