Similar Datasets
Project description:KLF10 deficiency in CD4+ T cells triggers obesity and insulin resistance
| PRJNA588090 | ENA
Project description:CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of CD4+ T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice and identified a predisposition to obesity, insulin resistance, and fatty liver due to defects of CD4+ Treg mobilization to liver and adipose tissue depots and decreased transforming growth factor β3 (TGF-β3) release in vitro and in vivo. Adoptive transfer of wild-type CD4+ Tregs fully rescued obesity, insulin resistance, and fatty liver. Mechanistically, TKO Tregs exhibit reduced mitochondrial respiration and glycolysis, phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR signaling, and consequently impaired chemotactic properties. Collectively, our study identifies CD4+ T cell KLF10 as an essential regulator of obesity and insulin resistance by altering Treg metabolism and mobilization.
| S-EPMC7816773 | biostudies-literature
Project description:Gene expression profiling of aortic tissue from WT and CD4-KLF10-KO mice injected once with the AAV-PCSK9D377Y gain-of-function transgene and placed on high cholesterol diet.
2023-02-03 | GSE196585 | GEO
Project description:Transcriptional profiling of mouse pancreatic cancer cells comparing Pdx-1Cre LSL-KrasG12D P53L/L cells with Pdx-1Cre LSL-KrasG12D KLF10L/L P53L/L cells, and to determine the effects of KLF10 deficiency on murine PDAC gene expression. Two-condition experiment, Pdx-1Cre LSL-KrasG12D P53L/L cells vs. Pdx-1Cre LSL-KrasG12D KLF10L/L P53L/L cells: 3 KLF10 wild type replicates, 3 KLF10 knockout replicates.
2016-08-22 | E-GEOD-85521 | biostudies-arrayexpress
Project description:Perivascular fibrosis, characterized by increased amount of connective tissue around vessels, is a hallmark for vascular disease. Angiotensin II (Ang II) contributes to vascular disease and end-organ damage via promoting T-cell activation. Despite recent data suggesting the role of T cells in the progression of perivascular fibrosis, the underlying mechanisms are poorly understood. Kruppel-like Factor 10 is a transcription factor expressed in T cell subsets. We sought to investigate the role of KLF10 in CD4+ T cells in regulating vascular damage in an AngII mouse model. CD4-targeted KLF10 deficient (TKO) and CD4-Cre (WT) mice were generated and subjected to 28 days of Ang II infusion. Differential gene expression profiling of non-stripped aorta, stripped aorta, isolated aortic fibroblasts from CD4-Cre (Cre) or CD4-Cre KLF10-fl/fl mice(TKO) mice after 28 days Angiotensin II (Ang II) treatment were performed to ascertain the underlying global transcriptomic changes involved in perivascular fibrosis. Since increased IL-9 is a profibrotic cytokine, we hypothesized that perivascular fibrosis might be rescued by administration of anti-IL-9 neutralizing monoclonal antibodies (mAbs) in Ang II-treated TKO mice. Then differential gene expression profiling of non-stripped aorta from TKO mice with or without anti-IL9-antibody treatment after 28 days Ang II infusion. To further understand the differences in phenotypic heterogeneity in fibroblasts during the progression of perivascular fibrosis between TKO and control mice in response to Ang II treatment, we performed single-cell RNA-sequencing (scRNA-seq) of the descending aorta. Collectively, comparative RNA-seq transcript profiling identified several pathways associated with periadventitial remodeling and that the calcium signaling pathway is dominantly upregulated in non-stripped aortas of TKO mice after Ang II treatment. Indeed, the profibrotic genes Col8a1, Mmp2, Fmod, and Angptl1, which were identified as significantly increased in TKO aortas and in isolated fibroblasts by both bulk RNA seq and scRNA seq, were all decreased after treatment with anti-IL-9 mAbs. These results indicate that the KLF10-IL-9 signaling axis in CD4+ T cells tightly regulate the processes of Ang II-induced pathological perivascular fibrosis and provide novel therapeutic opportunities for the treatment of hypertensive-associated diseases. 1) Differential gene expression profiling of non-stripped aotra, stripped aorta, aortic fibroblasts from CD4-Cre(Cre) or CD4-Cre KLF10-fl/fl mice(TKO) mice after 28 days Angiotensin II (Ang II) treatment. 2) Differential gene expression profiling of non-stripped aotra from TKO mice with or without anti-IL9-antibody treatment after 28 days Ang II infusion. 3) Single cell RNA-sequencing was perform on descending aorta from Cre or TKO after Ang II treatment.
2024-10-06 | GSE199288 | GEO
Project description:KLF10 deficiency in CD4+ T cells promotes atherosclerosis progression by altering macrophage dynamics
| PRJNA805540 | ENA
Project description:Experiment comparing the liver transcriptome from wild type and KLF10 deficient mice
2010-04-19 | E-MEXP-2089 | biostudies-arrayexpress
Project description:Exercise is recognized to be an effective way in the combat against obesity and related metabolic disorders, but the underlying mechanism is incompletely understood. Krüppel-like factor 10 (KLF10) is a transcription factor participating in diverse biological processes. KLF10 expression is abundant in adipose tissue, but its role in obesity is not well defined. Here, we show that exercise could facilitate adipocyte-derived KLF10 expression via the SIRT1/FOXO1 pathway. Adipocyte-specific knockout of KLF10 (KLF10AKO) blunts exercise-promoted white adipose browning, energy expenditure, fat loss, and glucose tolerance in diet-induced obese (DIO) mice. On the contrary, adipocyte-specific transgenic expression of KLF10 in mice (KLF10ATG) enhanced the abovementioned metabolic benefits induced by exercise. Mechanistically, KLF10 interacts with FOXO1 and facilitates the recruitment of KDM4A to form a ternary complex on the promoter regions of the Pnpla2 and Lipe genes to promote the expression of these key lipolytic genes, therefore facilitating lipolysis to defend against DIO in mice. As a newfound downstream effector responding to exercise, adipose KLF10 could act as a potential target in the fight against obesity
2024-08-25 | GSE269020 | GEO
Project description:Transcriptional profiling of mouse pancreatic cancer cells comparing Pdx-1Cre LSL-KrasG12D P53L/L cells with Pdx-1Cre LSL-KrasG12D KLF10L/L P53L/L cells, and to determine the effects of KLF10 deficiency on murine PDAC gene expression.
2016-08-22 | GSE85521 | GEO
Project description:KrÜppel-like factor 10 (KLF10), deficient in two thirds of 105 resected pancreatic adenocarcinoma (PDAC) patients, was associated with rapid loco-regional recurrence and large tumor size. Additional KLF10 depletion in KC (LSL: KrasG12D; Pdx1-CRE) mice accelerated progression from pancreatic intraepithelial neoplasia to PDAC. In Panc-1 cells with KLF10 deficiency (Panc-1-pLKO-shKLF10), increased sphere formation, stem cell markers expression, and tumor growth were noted compared with those of control. Over-expressing KLF10 genetically or pharmacologically using metformin, reversed the stem cell phenotypes induced by KLF10 depletion. Ingenuity pathway analysis and gene set enrichment analysis showed Notch signal molecules including Notch receptors 3 and 4 were over-expressed in Panc-1-pLKO-shKLF10. KLF10 transcriptionally suppressed Notch 3 and 4 receptors by competing with ELF3, a positive regulator, for promoter binding. Downregulating Notch signal genetically or pharmacologically ameliorated stem cell phenotypes of Panc-1-pLKO-shKLF10. Elevating KLF10 expression by metformin with concomitant evodiamine, a non-toxic Notch 3 methylation stimulator, delayed murine tumor growth of PDAC with KLF10 deficiency without prominent toxicity. These results demonstrated a novel signal pathway of KLF10 in modulating stem cell phenotypes of PDAC via transcriptional regulating Notch signal pathway. Elevating KLF10 and suppressing Notch signal may cooperatively reduce PDAC tumorigenesis and malignant progression.
2023-06-21 | GSE218172 | GEO