Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13197315_1.fastq.gz | Fastqsanger.gz | |||
| SRR13197315_2.fastq.gz | Fastqsanger.gz | |||
| SRR13197316_1.fastq.gz | Fastqsanger.gz | |||
| SRR13197316_2.fastq.gz | Fastqsanger.gz | |||
| SRR13197317_1.fastq.gz | Fastqsanger.gz |
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Project description:Epigenetic changes deregulate gene expression to drive oncogenesis. The reversible nature of these changes enables therapeutic targeting, as in cutaneous T-cell lymphoma (MF/SS), Histone deacetylase inhibitors (HDACi), which alter epigenetic modifications, are effective in ~30% of MF/SS patients. However, there are no markers that predict MF/SS progression or therapy resistance. We hypothesized that epigenetic alterations drive MF/SS progression and promote HDACi drug resistance. Therefore, we profiled the epigenomes and transcriptomes of malignant T cell purified from skin biopsies and peripheral blood from MF/SS patients (N=21) before and after treatment with HDACi, as well as in vitro HDACi-treated CD4+ T cells from healthy donors. Here we report for the first time the epigenome-wide map of acetylation changes in MF/SS patients treated with HDACi, and define the significant differences in regulatory element activity and corresponding transcriptional changes in HDACi-sensitive versus resistant tumors. Our studies identified genes not previously associated with MF/SS, nor with disease progression or HDACi resistance, and were enriched in pathways that regulate apoptosis (BIRC5), cell cycle (RRM2), and chromosome cohesion (CENPH). We also identified a striking number of genes whose products are involved in cell adhesion and migration, including CCR6, LAIR2, VCAM1, and EPCAM. The mRNA of LAIR2, which encodes a receptor protein secreted by activated T cells that binds collagen and prevents binding of the inhibitory receptor LAIR1, was significantly upregulated in MF/SS tumors that were resistant to HDACi therapy and manifested in both skin and peripheral blood. We also detected elevated levels of LAIR2 protein in the plasma of MF/SS patients with progressive disease. Taken together, these studies defined the first epigenome-wide acetylation landscape of HDACi responsive and resistant MF/SS tumors, identified significantly altered patterns of epigenetic regulation and corresponding gene expression in HDACi resistant MF/SS tumors, and connected them to novel pathways of disease progression, particularly in cell adhesion and migration. These findings may represent novel predictive markers for MF/SS progression that are also targets for future therapeutic development.
2019-08-09 | GSE132053 | GEO
Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans.
2016-01-01 | GSE69670 | GEO
Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.
2019-08-26 | GSE127000 | GEO
Project description:The current study aimed to investigate whether bovine non-coding RNA play a role in regulating E. coli O157 shedding through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 to 413 ± 49. Compared between SS and NS, the number of differentially expressed (DE) miRNAs ranged from one to eight, and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (8 and 7, respectively). Functional analysis indicated that the bta-miR-378b, bta-miR-2284j and bta-miR-2284d which were down-regulated in both distal jejunum and rectum of SS, the bta-miR-2887 which was down-regulated in rectum of SS, as well as the bta-miR-211 and bta-miR-29d-3p which were up-regulated in rectum of SS were potentially regulatory to host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that the alternation of miRNA expression in the gut of SS may lead to differential regulation in immune functions involved in E. coli O157 super-shedding in cattle.
2018-10-30 | GSE121916 | GEO
Project description:The current study aimed to investigate whether bovine non-coding RNA play a role in regulating E. coli O157 shedding through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 to 413 ± 49. Compared between SS and NS, the number of differentially expressed (DE) miRNAs ranged from one to eight, and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (8 and 7, respectively). Functional analysis indicated that the bta-miR-378b, bta-miR-2284j and bta-miR-2284d which were down-regulated in both distal jejunum and rectum of SS, the bta-miR-2887 which was down-regulated in rectum of SS, as well as the bta-miR-211 and bta-miR-29d-3p which were up-regulated in rectum of SS were potentially regulatory to host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that the alternation of miRNA expression in the gut of SS may lead to differential regulation in immune functions involved in E. coli O157 super-shedding in cattle.
2018-12-01 | GSE96973 | GEO
Project description:Disease-causing aberrations of childhood cancers recurrently target the chromatin pathway genes leading to epigenetic dysregulation. For example, almost 100% of patients with synovial sarcoma (SS) carry an abnormal gene fusion termed SS18-SSX, which produces a disease-specific oncofusion protein that is incorporated into the SWI/SNF chromatin-remodeling complex and profoundly alters its functionalities. Thus, targeting epigenetic dependencies in childhood cancer holds great promise for improving current treatment of the affected patients. Leveraging on the cancer cell dependency dataset, medicinal chemistry tool compounds and genomic profiling approaches, we here show WDR5, a chromatin factor involved in the deposition of histone H3 lysine 4 (H3K4) methylation, to be an unexplored vulnerability of SS. Mechanistically, WDR5 and SS18-SSX associate with one another and colocalize significantly at the target oncogenes where WDR5 is essential for optimal chromatin binding of the SS18-SSX-containing chromatin modelers. Using the WDR5-targeted Proteolysis Targeting Chimera (PROTAC) compound, we further show that pharmacologic degradation of WDR5 in SS cells not only suppressed the SS18-SSX-related oncogenic gene-expression programs but additionally led to p53 activation and tumor cell senescence through downregulation of ribosomal proteins (RPs) and activation of nucleolar stress response. Importantly, the WDR5-targeted PROTAC significantly suppressed malignant growth of SS in vitro and in vivo. Taken together, we report WDR5 as a SS dependency and demonstrate the WDR5 PROTAC degrader to be a promising strategy for the treatment of SS.
2025-04-02 | GSE287557 | GEO
Project description:Disease-causing aberrations of childhood cancers recurrently target the chromatin pathway genes leading to epigenetic dysregulation. For example, almost 100% of patients with synovial sarcoma (SS) carry an abnormal gene fusion termed SS18-SSX, which produces a disease-specific oncofusion protein that is incorporated into the SWI/SNF chromatin-remodeling complex and profoundly alters its functionalities. Thus, targeting epigenetic dependencies in childhood cancer holds great promise for improving current treatment of the affected patients. Leveraging on the cancer cell dependency dataset, medicinal chemistry tool compounds and genomic profiling approaches, we here show WDR5, a chromatin factor involved in the deposition of histone H3 lysine 4 (H3K4) methylation, to be an unexplored vulnerability of SS. Mechanistically, WDR5 and SS18-SSX associate with one another and colocalize significantly at the target oncogenes where WDR5 is essential for optimal chromatin binding of the SS18-SSX-containing chromatin modelers. Using the WDR5-targeted Proteolysis Targeting Chimera (PROTAC) compound, we further show that pharmacologic degradation of WDR5 in SS cells not only suppressed the SS18-SSX-related oncogenic gene-expression programs but additionally led to p53 activation and tumor cell senescence through downregulation of ribosomal proteins (RPs) and activation of nucleolar stress response. Importantly, the WDR5-targeted PROTAC significantly suppressed malignant growth of SS in vitro and in vivo. Taken together, we report WDR5 as a SS dependency and demonstrate the WDR5 PROTAC degrader to be a promising strategy for the treatment of SS.
2025-04-02 | GSE272211 | GEO
Project description:Sjogren's syndrome (SS) dry eye is a chronic autoimmune eyedisease driven by T helper 17 (Th17)cells. S100A8/A9 has emerged as an important proinflammatory alarmin in variousautoimmune and inflammatory diseases. However, the role of S100A8/A9 in the pathogenesis of SS dry eye remains unexplored. Here,we show that the expression levels of S100A8/A9 were elevated in peripheral blood mononuclear cells (PBMCs) of patients with SS dry eye, as well as the lacrimal glands (LGs) of SS dry eye mice. The administration of paquinimod, a specific inhibitor of S100A8/A9, could alleviate the progression of SS dry eye with significant reduction of Th17 cell frequency in LGs, spleen and lymph nodes of SS dry eye mice.Further experiment revealed that S100A8/A9 did not directly affect Th17 generation and function, but upregulated the expression of MHCIl andI123a in DCs to augment Th17 cell response through a Acod1/STAT3-dependent signaling pathway in the context of SS dry eye. Together,these findings unveiled the key role of S100A8/A9 in the pathogenesis of SS dry eye and suggested a potential therapeutic avenue for SS dry eyeand otherTh7 cell-related autoimmune disorders.
2025-01-22 | GSE276800 | GEO
Project description:WGS of Streptococcus porcinus SS-841, Streptococcus pseudoporcinus SS-607 and SS-662.
| PRJEB16023 | ENA