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:WGS of Streptococcus porcinus SS-841, Streptococcus pseudoporcinus SS-607 and SS-662.
| PRJEB16023 | ENA
Project description:Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect in patients. Because ATR governs DNA repair response, the mutation has been considered the cause of an impaired response to DNA replication stress in neuronal progenitor cells (NPCs), which is associated with the pathogenesis of microcephaly. However, the precise mechanism through which the mutation causes SS remains unclear. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone by genome editing. Interestingly, SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs. In SS-NPCs, abnormal mitotic spindles were observed more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that a CLK1 inhibitor, TG003, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Furthermore, treatment with TG003 restored the function of ATR in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model of SS revealed a novel function of the ATR mutation in NPCs and NPC-specific missplicing, proving its usefulness for dissecting the pathophysiology of ATR-SS.
2019-02-28 | GSE121384 | GEO
Project description:Modified Vaccinia Ankara (MVA) was recently approved as a Smallpox vaccine. Transmission of Variola is by respiratory droplets, and MVA delivered by skin scarification (ss) protected mice far more effectively against lethal respiratory challenge with VACV than any other route of delivery, and at much lower doses. Comparisons of ss with intradermal, subcutaneous or intramuscular routes showed that MVAOVA ss-generated T cells were both more abundant and transcriptionally distinct. MVAOVA ss produced greater numbers of lung Ova-specific CD8+ TRM and was superior in protecting mice against lethal VACVOVA respiratory challenge. Nearly as many lung TRM were generated with MVAOVA ss compared to direct pulmonary immunization with MVAOVA, and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVA ss-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via direct pulmonary immunization. Overall, our data suggest that heterologous MVA vectors delivered via ss are uniquely well-suited as vaccine vectors for respiratory pathogens like COVID-19. In addition, MVA delivered via ss could represent a more effective dose-sparing smallpox vaccine.
2020-05-10 | GSE150190 | GEO
Project description:Splice site strength and the presence of splicing regulatory elements (SREs) play central roles in the control of pre-mRNA splicing1-3 and in exon evolution4. However, the degree to which SRE function is dependent or independent of the strength of nearby splice sites is not well understood. Here, we show that the activity of a major class of mammalian SREs is highly sensitive to the strength of the adjacent 5' splice site (5'ss) sequence, with important functional and evolutionary implications. Using extensive splicing reporter assays, we found that activity of identical 'G-run' intronic splicing enhancers (ISEs)5, 6 was higher by ~4-fold for 5'ss of intermediate strength relative to weak 5'ss, and higher by ~1.3-fold relative to strong 5'ss, based on established 5'ss scoring criteria7. This dependence on 5'ss strength was supported both by comparative genomic analyses and by high-throughput transcriptome sequencing analyses of splicing changes following RNAi against the G-run-binding factor heterogeneous nuclear ribonucleoprotein (hnRNP) H. This pattern and an inverse pattern of 5'ss-dependent activity observed for G-run exonic splicing silencers (ESSs) enables G-runs and hnRNP H to buffer 5'ss mutations and to function as effective evolutionary capacitors8 of splicing change. Human exons flanked by G-runs exhibited increased 5'ss polymorphism and a ~30% increased frequency of evolutionary change between constitutive and alternative splicing, supporting a role in facilitating splicing-level evolution. Evolutionary conservation indicated a substantially greater role for intronic elements generally in splicing of exons with weak and intermediate 5'ss, and supported 5'ss strength-dependent activity for several other intronic motifs, suggesting widespread functional and evolutionary differences between exons of differing 5'ss strength. Keywords: gene expression array-based, exon and protein coding gene analysis
2009-09-13 | GSE12386 | GEO
Project description:We systematically explored the transcriptome of 10 synovial sarcoma (SS) patients. We detected a large number of upregulated and downregulated genes in SS compared to normal tissues, which were mainly involved in cell cycle, metabolic and P53 signaling pathways. Moreover, we identified a multitude of differentially alternative spliced genes, indicating that the deregulation of alternative splicing could be one of main factors contribute to the tumorigenesis of SS. A set of tumor-specific gene fusion pairs were identified in SS. We also detected dozens of differentially expressed circRNAs and their parental genes were enriched in muscle related biological process. The interaction network constructed based on circRNAs, miRNAs and corresponding target genes showed that the differentially expressed circRNAs in SS have the potential to regulate the expression of a number of SS related genes. Collectively, we systematically investigated the abnormal expression profile of SS and gain insights into the molecular mechanism from different views of transcriptome expression changes.
2022-02-01 | GSE144190 | GEO