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Transcriptomic Profiling of Scleroderma Monocytes Reveals Links with Cardiovascular Complications, Implicating Notch and Interferon Pathways

ABSTRACT: Transcriptomic Profiling of Scleroderma Monocytes Reveals Links with Cardiovascular Complications, Implicating Notch and Interferon Pathways

PROVIDER: PRJNA1295412 | ENA |

REPOSITORIES: ENA

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Transcriptomic Profiling of Scleroderma Monocytes Reveals Links with Cardiovascular Complications, Implicating Notch and Interferon Pathways

Project description:Objectives: Recent research has highlighted the critical role of monocytes and macrophages in driving both inflammatory and fibrotic processes in systemic sclerosis (SSc). This study seeks to elucidate the gene expression profiles of SSc monocytes and their potential links to disease complications, with the ultimate goal of uncovering novel therapeutic targets. Methods: 48 SSc patients and 15 controls were recruited and monocytes were isolated using CD14+ magnetic beads. Total RNA was extracted and bulk RNA-seq analysis was performed. Differential gene expression followed by unsupervised hierarchical clustering and pathway analysis were conducted and correlations with clinical features were analyzed. Interferon signature score (IFN6) was calculated using the log transformed values of 6 genes (IFIT3, IFIT2, MX1, IFIH1, STAT2, and NCF1). Results: We identified four distinct patient subgroups, relative to normal, two with inflammatory and two with non-inflammatory gene profiles. The inflammatory subgroups exhibited high expression of interferon-related genes and included all SSc patients with pulmonary hypertension and most with cardiac involvement. In these patients, IFN6 was markedly elevated and showed a significant correlation with global longitudinal strain - GLS (r=-0.5, p=0.006), a key indicator of cardiac function. Furthermore, pathway analysis identified an enrichment of the Notch signaling pathway among genes whose overexpression correlated with impaired GLS. Conclusion: These findings unveil a potential new mechanistic link between interferon activity, Notch signaling, and cardiac complications in SSc, offering new insights into disease pathogenesis and potential therapeutic targets.

2025-08-01 | GSE303431 | GEO

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Transcription profiling of human skin bioposis from patients with diffuse scleroderma and limited scleroderma

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

Scleroderma Morphea Normal Fibroblasts

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

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