Expression data from mouse CD4+ T cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59241 | GEO | 2015/07/22
SECONDARY ACCESSION(S): PRJNA254800
REPOSITORIES: GEO
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Project description:Hydrogen sulfide (H2S) is an endogenous gasotransmitter and is capable of regulating various endogenous signaling pathways, inculding inflamation and immune response. In mammals, H2S is mainly generated by two pyridoxal-5’-phosphate-dependent enzymes, termed cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). CBS-deficient mice showed autoimmune disorders. H2S play important roles in T cell development and differentiation, especially Treg cells development and differentiation. We used microarrays to detail the global gene expression of WT and CBS-deficient CD4+ T cells. CD4+ T cells from WT and CBS-deficient mice were isolated for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the homogeneous populations of mice at 6 weeks in order to increase the temporal resolution of expression profiles.
2015-07-22 | E-GEOD-59241 | biostudies-arrayexpress
Project description:The gasotransmitter hydrogen sulfide (H2S), produced by transsulfuration pathway, in recent years has been recognized as a biological mediator playing important role under normal conditions and in various pathologies both in eukaryotes and prokaryotes. The transsulfuration pathway (TSP) includes the conversion of homocysteine to cysteine following the breakdown of methionine. In Drosophila melanogaster and other eukaryotes H2S is produced by cystathionine B-synthase (CBS), cystathionine y-lyase (CSE), and 3-mercaptopyruvate sulftransferase (MST). In the experiments reported here we were able exploring CRISPR technique to obtain single and double deletions of these three major genes responsible for H2S production. In most cases the deletion of one studied gene does not result in the compensatory induction of two other genes responsible for H2S production. Transcriptomic studies demonstrated that the deletions of the above genes alter the genome expression to different degree with more pronounced effect exerted by deletions of CBS gene. Furthermore, the double deletion of both CBS and CSE resulted in cumulative effect on the transcription in the resulted strains. Overall, we found that the obtained deletions affected numerous genes involved in various biological pathways. Characteristically, genes involved in oxidative reduction process, stress-response genes, house-keeping genes, genes participating in olfactory and reproduction were among the most affected. Furthermore, characteristic differences in the response to the deletions of the studied genes were apparently organ specific and have clear-cut gender character. Importantly, the deletions altered global methylation and chromatin state of the experimental strains by increasing the level of inactive chromatin of the genome. Single and double deletions of the three genes responsible for the production of H2S helped to understand new aspects of biological significance of this vital physiological mediator.
2020-04-07 | GSE148109 | GEO
Project description:The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognised to play a crucial role in human health. However, a role for host H2S in pathogenesis has not yet been demonstrated. Using cystathionine -lyase (CSE) deficient mice, we demonstrated an unexpected role of H2S in Mtb pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than wild-type mice, and support reduced pathology and lower bacterial burdens in the lung, spleen and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units (CFUs) in CSE-/-cells. Chemical complementation of infected wild-type and CSE-/-macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response and reduces circulating IL1β, IL-6, TNFα, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected wild type mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1β, IL-6 and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S producing enzymes in human necrotic, non-necrotic and cavitary pulmonary TB lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
2020-04-06 | GSE143619 | GEO
Project description:CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumour suppressors. Currently, for most cancers including gastric cancer [GC], mechanisms underlying CIMP remain poorly understood. We sought to discover molecular contributors to CIMP in GC, by performing global DNA methylation, gene expression, and proteomics profiling across 14 gastric cell lines, followed by similar integrative analysis in 50 GC cell lines and 467 primary GCs. We identify the cystathionine beta-synthase enzyme (CBS) as a highly recurrent target of epigenetic silencing in CIMP GC. Likewise, we show that CBS epimutations are significantly associated with CIMP in various other cancers, occurring even in premalignant gastroesophageal conditions and longitudinally linked to clinical persistence. Of note, CRISPR deletion of CBS in normal gastric epithelial cells induces widespread DNA methylation changes that overlap with primary GC CIMP patterns. Reflecting its metabolic role as a gatekeeper interlinking the methionine and homocysteine cycles, CBS loss in vitro also causes reductions in the anti-inflammatory gasotransmitter hydrogen sulphide (H2S), with concomitant increase in NF-κB activity. In a murine genetic model of CBS-deficiency, preliminary data indicate upregulated immune-mediated transcriptional signatures in the stomach. Our results implicate CBS as a bi-faceted modifier of aberrant DNA methylation and inflammation in GC and highlights H2S donors as a potential new therapy for CBS-silenced lesions.
2021-04-19 | GSE149411 | GEO
Project description:To reveal the role of sulfur metabolism genes in memory formation processes, transcriptome libraries were obtained from the heads of 5-day-old naive males. The libraries were generated from Drosophila strains created in our laboratory with deleted cbs genes ( CBS-/-(5) and CBS-/-(8), cse (CSE-/-) and strains with double deletion of cbs and cse genes (CBS-/-,CSE-/-(1) and (CBS-/-,CSE-/-(2). Strain 58492, in which deletions were introduced by the CRISP/CAS9 method, was used as a control strain.
2022-04-14 | GSE200397 | GEO
Project description:The cumulative role of cellular organelle’s in shaping the life and function of a cell has been long acknowledged. While each organelle plays a specific role in the growth and development of T cells, numerous studies have thus far focused on targeting mitochondria, endoplasmic reticulum, or lysosome related pathways to improve anti-tumor T cell immune response. Here we highlight the tumor microenvironment (TME) mediated disruption of Golgi architecture and function, termed Golgi stress, contributes to altered redox signaling and affects cell survival. Importantly, the decreased expression if GM130, a marker of Golgi stress and indicating the disruption of Golgi architecture, was reverted upon treatment with hydrogen sulphide (H2S) donor GYY4137, or over expressing cystathionine β-synthase (Cbs), an enzyme involved in biosynthesis of endogenous H2S. Activation and expansion of tumor reactive TCR or chimeric antigen receptor bearing T cells expanded with exogenous H2S promoted stemness, antioxidant capacity and exhibited an increase effector cytokine secretion that correlated to increased protein translation. In in vivo models of melanoma and lymphoma, anti-tumor T cells conditioned ex vivo with exogenous H2S or overexpressing Cbs demonstrated superior tumor control upon ACT. Further, sorting anti- tumor T cells based on Golgi structure and abundance resulted in identification of a Golgihi subset of T cells with a unique metabolic signature, superior fitness, and enhanced anti-tumor capacity. These data suggest that H2S can be used an immunomodulatory agent to enhance the efficacy of ACT, and that the structure and function of the Golgi apparatus is an important feature of T cells that determines their anti-tumor capacity.
2024-11-20 | GSE249287 | GEO
Project description:Hydrogen sulfide (H2S) as an important gasotransmitter has fundamental roles in human diseases. The cellular effect of H2S has received lots of attention recently. H2S can affect ion channels, transcription factors and kinase in mammals. The mechanism of cellular effect of H2S is not completely understood. We used fission yeast as a model organism to study the global transcriptional profile in response to H2S by microarray.
2012-06-15 | GSE30025 | GEO
Project description:We use stable expression of a cystathionine-beta synthase (CBS) variant library in HEK293T cells to identify CBS coding sequence variants that alter mRNA abundance
2022-04-22 | GSE201057 | GEO
Project description:Ginseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionin beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (HRR2RRS) synthesis in the liver. This investigation provides novel evidence that14T sub-chronic administration of 4T14TKRG can elevate HRR2RRS production by increasing protein expression of CBS and CSE in the liver.
2021-09-10 | PXD023731 | Pride
Project description:Since both endogenous synthesis in tumor cells and bacterial sulfur reduction activities are sources of H2S in colon cancer microenvironment, in addition to using CBS -/+ mice, we also investigated the roles of reducing H2S through adopting a sulfur amino acid restriction diet (SARD) (0.15% methionine and 0% cystine) on immunotherapy (anti-PD-L1) of colon cancer. Tumor bulk sequencing was performed in cecum orthotopic CT26 tumors collected from IgG and anti-PD-L1 treated mice both receiving normal diet and SARD.
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