The UCSD O'Connor TSP (TwinSiblingPedigree) Resource in Hypertension
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PROVIDER: PRJNA671474 | ENA |
REPOSITORIES: ENA
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Project description:The UCSD O'Connor TSP (TwinSiblingPedigree) Resource in Hypertension
| PRJNA671473 | ENA
Project description:Schistosomiasis, a prevalent cause of pulmonary hypertension (PH) globally, triggers type 2 inflammation, with interstitial macrophages (IMs) derived from monocytes playing a crucial role. These IMs produce thrombospondin-1 (TSP-1), activating TGF-β and driving PH pathology. Two distinct IM subpopulations were identified: resident FOLR2+ IMs expressing monocyte recruitment factors, and recruited CCR2+ IMs expressing TSP-1. Upon exposure to Schistosoma, the CCR2+ subpopulation expanded. Flow cytometry and single-cell RNA sequencing confirmed these findings, revealing crosstalk between IM subpopulations. The resident FOLR2+ IMs increased expression of monocyte recruitment ligands, while the recruited CCR2+ IMs expressed elevated TSP-1, activating TGF-β and contributing to PH. This study provides insights into the complex interplay of IM subpopulations in Schistosoma-induced PH, shedding light on potential therapeutic targets for this global health concern.
2024-05-08 | GSE254338 | GEO
Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.
2022-07-27 | PXD034065 | Pride
Project description:We examined the gene expression profiles of CD4+ T-cells isolated from 7 ATL, 12 HAM/TSP and 11 AC (asymptomatic carriers) to identify gene signatures that may be characteristic for these particular diseases. Using gene expression arrays, we identified ~ 1039 immune-related genes that were differentially expressed in CD4+ T cells; using stringent exclusion criteria, a 122 gene signature could be divided into 3 groups: I) ATL-specific; II) common; and III) HAM/TSP-specific markers To better understand the genetic differences between HTLV-1-associated diseases, we examined the gene expression profile of T lymphocytes from patients either suffering from ATL, HAM/TSP or carrying the HTLV-1 virus without any symptoms. Microarray experiments were performed using the human ImmuneArray cDNA array (UHN Microarray Center, University of Toronto). We used the Stratagene Universal Control, labelled Cy5 for all samples in a competitive hybridization.
2010-02-13 | E-GEOD-19080 | biostudies-arrayexpress
Project description:We examined the gene expression profiles of CD4+ T-cells isolated from 7 ATL, 12 HAM/TSP and 11 AC (asymptomatic carriers) to identify gene signatures that may be characteristic for these particular diseases. Using gene expression arrays, we identified ~ 1039 immune-related genes that were differentially expressed in CD4+ T cells; using stringent exclusion criteria, a 122 gene signature could be divided into 3 groups: I) ATL-specific; II) common; and III) HAM/TSP-specific markers
2010-02-14 | GSE19080 | GEO
Project description:Human Developmental Biology Resource (HDBR) expression resource-RNAseq
| PRJEB14594 | ENA
Project description:Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. Recently, we and others have proposed that HTLV-1 preferentially infects CD4+CD25+CCR4+ T-cells. In this study, we used microarrays to examine the gene expression profiles of CD4+CD25+CCR4+ T-cells isolated from a HAM/TSP patient, an ATLL patient and a healthy donor to identify gene signatures that may be characteristic for these particular diseases.
2017-08-29 | GSE57259 | GEO
Project description:Background: Urethral stricture is related to scar tissue fibrosis, but its pathogenesis is still unclear. This study aims to explore the mechanism of circular RNA (circRNA) in the occurrence and development of urethral stricture. Methods: CircRNA microarray was employed to analyze circRNA expression profiles between human urethral scar tissue and normal urethral tissue. The first nine circRNA differentially expressed were selected for RT-qPCR detection. Urethral scar fibroblasts were isolated from human urethral scar tissue and cultured in vitro. The cells were transfected with si-circ_0047339, LV-circ_0047339, and miR-4691-5p mimic and their corresponding negative controls. Related gene and protein expression was measured by RT-qPCR, Western Blot and immunofluorescence staining, and the cell function was detected by CCK-8 and EDU assay. The targeting relationship between miR-4691-5p and circ_0047339 or TSP-1 was analyzed by dual-luciferase reporter assay. Results: The results of circRNA microarray showed that there were 268 differential genes between urethral scar tissue and normal urethral tissue (circRNA expression difference multiple ≥2 and p value≤0.05). The enrichment analysis of KEGG (Kyoto encyclopedia of genes and genomes) showed that these circRNAs were significantly correlated with ECM-receptor interaction. The first nine differentially expressed circRNA were selected to predict the circRNA-miRNA network. RT-qPCR results showed that circ_0047339 was upregulated considerably in urethral scar tissue. After silencing circ_0047339, the proliferation of urethral scar cells decreased significantly, and the expression of collagen 1 (COL-1) and α-smooth muscle actin (α-SMA) also reduced. Circ_0047339 as a competing endogenous RNA (ceRNA) could increase the expression of TSP-1 by competitively binding miR-4691-5p. In addition, miR-4691-5p mimic transfection could inhibit the proliferation of urethral scar fibroblasts and the presentation of thrombospondin-1 (TSP-1), α-SMA and COL-1, while circ_0047339 overexpression eliminated this inhibition. Conclusion: Our results showed that the dysfunctional circ_0047339 might promote the growth and fibrosis of urethral scar fibroblasts through the ceRNA mechanism, thus promoting the development of urethral stricture via miR-4691-5p/TSP-1 axis.
2022-07-30 | GSE209937 | GEO