Transcriptional profiles of CD27 negative and positive MAIT cells from PBMC of diabetic obese patients
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PROVIDER: PRJNA777453 | ENA |
REPOSITORIES: ENA
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Project description:Our previous observation found CD27 negative MAIT cell subset is associated with T2D progression in overweight/obese patients. To identify the difference of functional properties between CD27 negative and positive MAIT subsets under obesity related T2D condition, we isolated circulating CD27+ or CD27- CD3+ CD161+ TCR Va7.2+ MAIT cells from PBMC of three diabetic obese patients and performed bulk RNA-seq based on Smart-seq2 protocol. By the comparison of CD27- and CD27+ MAIT cells, we found CD27- MAIT cell exhibit an increased mitochondrial mass and decreased response to bacterium transcriptional pattern compared to CD27+ MAIT cells in diabetic obese patients, indicating the imbalanced cell-bacteria interaction might contribute to T2D progression in overiweight/obese people.
2022-05-24 | GSE187349 | GEO
Project description:Investigating the protein and gene profiles of tumor-infiltrating MAIT cells compared to PBMC from CRC patients
2020-06-05 | GSE151842 | GEO
Project description:Obesity underpins the development of numerous chronic diseases such as type II diabetes mellitus. It is well established that obesity negatively alters immune cell frequencies and functions. Mucosal Associated Invariant T (MAIT) cells are a population of innate T cells, which we have previously reported are dysregulated in obesity, with altered circulating and adipose tissue frequencies and a reduction in their IFN-gamma production, which is a critical effector function of MAIT cells in host defence. Hence there is increased urgency to characterise the key molecular mechanisms that drive MAIT cell effector functions, and to identify those which are impaired in the obesity setting. In this study, we found that MAIT cells significantly upregulate their rates of glycolysis upon activation in an mTORC1 dependent manner and this is essential for MAIT cell IFN-g production. Furthermore, we show that mTORC1 activation is dependent on amino acid transport via SLC7A5. In obese patients, using RNA sequencing, Seahorse analysis and a series of in vitro experiments, we demonstrate that MAIT cells isolated from obese adults display defective glycolytic metabolism, mTORC1 signalling and SLC7A5 amino acid transport. Collectively our data details the intrinsic metabolic pathways controlling MAIT cell cytokine production and highlights mTORC1 as an important metabolic regulator that is impaired in obesity, leading to altered MAIT cell responses. We report on MAIT cells isolated from lean and obese adults
2019-04-16 | GSE126169 | GEO
Project description:The aim of study was to investigate correlation bewteen peripheral blood mononuclear cell (PBMC) transcriptome profiles and plasma lipid profiles of Korean adult with varying BMI. In Korean, BMI cut-off points are 18.5~22.9 kg/m2 (normal range), ≥ 23 kg/m2 (overweight), ≥ 25 kg/m2 (obese), ≥ 30 kg/m2 (severely obese). Thus, the obese group was subdivided into mildly obese (BMI 25~27 kg/m2, OA) and highly obese (BMI 27~30 kg/m2, OB). This study indicates that lipid, glucose and inflammation metabolism-related gene expressions were altered according to cahnge of varing phenotype biomarkers such as BMI, plasma total-C, TG, FFA and HDL-C. Thus, blood biomarkers and PBMC gene expression profiles identified in this study may be useful as indicative biomarkers for obese susceptibility in Korean adult as well as response to various intervention for treating obesity.
2014-06-01 | GSE55205 | GEO
Project description:The aim of study was to investigate correlation bewteen peripheral blood mononuclear cell (PBMC) transcriptome profiles and plasma lipid profiles of Korean adult with varying BMI. In Korean, BMI cut-off points are 18.5~22.9 kg/m2 (normal range), M-bM-^IM-% 23 kg/m2 (overweight), M-bM-^IM-% 25 kg/m2 (obese), M-bM-^IM-% 30 kg/m2 (severely obese). Thus, the obese group was subdivided into mildly obese (BMI 25~27 kg/m2, OA) and highly obese (BMI 27~30 kg/m2, OB). This study indicates that lipid, glucose and inflammation metabolism-related gene expressions were altered according to cahnge of varing phenotype biomarkers such as BMI, plasma total-C, TG, FFA and HDL-C. Thus, blood biomarkers and PBMC gene expression profiles identified in this study may be useful as indicative biomarkers for obese susceptibility in Korean adult as well as response to various intervention for treating obesity. Total RNA of PBMCs was obtained from normal weight, obese person and mRNA expression was measured.
2014-06-01 | E-GEOD-55205 | biostudies-arrayexpress
Project description:Type 2 diabetes is a complex disease associated with many underlying pathomechanisms. Epigenetic regulation of gene expression by DNA methylation has become increasingly recognized as an important component in the etiology of type 2 diabetes. We performed genome-wide methylome and transcriptome analysis in liver from severely obese patients with or without type 2 diabetes to discover aberrant pathways underlying the development of insulin resistance. We identified hypomethylation of five key genes involved in hepatic glycolysis, de novo lipogenesis and insulin resistance with concomitant increased mRNA expression and protein content. The CpG-site within the ATF-motif was hypomethylated in four of these genes in liver of non-diabetic and type 2 diabetic obese patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. In conclusion, severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome and genes controlling glucose and lipid metabolism are hypomethylated at a regulatory site. Thus, obesity may epigenetically reprogram the liver towards increased lipid production and exacerbate the development of insulin resistance. To better understand the molecular mechanisms underlying the development of hepatic insulin resistance and type 2 diabetes at a molecular level, we performed a genome-wide methylome and transcriptome analysis of liver from non-obese metabolically healthy, obese non-diabetic and obese type 2 diabetic patients. Distinct DNA methylation and gene expression profiles were identified in liver from the obese and type 2 diabetic patients compared with the non-obese participants.
2016-03-08 | E-GEOD-64998 | biostudies-arrayexpress
Project description:To show the similarity among MAIT-iPSCs, hiPSCs and hESCs and the gradual change of global gene expression of reMAIT cells along with differentiation, this experiment was designed. MAIT cells, MAIT-iPSCs, hiPSCs, hESCs, MAIT cells, and reMAIT cells at the several differerent stages of differentiation were collected. Then, they were applied in this experiment.
2013-03-21 | E-GEOD-44559 | biostudies-arrayexpress
Project description:Type 2 diabetes mellitus (TM) is a severely metabolic disorder that affects above 10% worldwide population. Obesity is a major cause of insulin resistance and contributes to the development of TM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. Nonhuman primate (NHP) rhesus monkey is an appropriate animal for research of human diseases. Here, we first screened and selected three individual spontaneous and diabetic rhesus monkeys. Interestingly, the diabetic monkeys were obese with high BMI at beginning, but gradually lost their body weight during one-year observation. Furthermore, we performed a SILAC-based quantitative proteomics to identify proteins and signaling pathways with altered expression in the liver of obese and diabetic monkeys. Totally, 3509 proteins were identified and quantified, and of which 185 proteins displayed altered expression level. GO analysis revealed that the expression of proteins involved in fatty acids β-oxidation and galactose metabolism was increased in obese monkeys; while proteins involved in oxidative phosphorylation (OXPHOS) and branched chain amino acid (BCAA) degradation was upregulated in diabetic monkeys. In addition, we observed a mild impaired mitophagy and apoptosis in the liver of diabetic monkeys, suggesting a dysfunction of mitochondria and liver injury in the late onset of diabetics. Taken together, our liver proteomics may reveal a distinct metabolic transition from fatty acids β-oxidation in obese monkey to BCAA degradation in diabetic monkeys.
2019-08-26 | PXD008825 | Pride
Project description:At variance with what is observed in mice, no distinct MAIT1 or MAIT17 subsets exist in human blood, as all MAIT cells express a variety of transcription factors such as Rorgt, Tbet, Eomes and Helios. However, they are also found in tissues in which they have specific effector functions. To determine these tissue programs, we analyzed the transcription pattern of MAIT cells as compared to mainstream memory (CD45RA-CD27+) CD4+ and CD8+ T cells from human blood and liver. The paired samples of blood and liver cells were obtained from patients operated for metastatic uveal melanoma (liver samples from a “healthy” liver fragment), and from the blood of healthy controls.
2018-12-03 | E-MTAB-7143 | biostudies-arrayexpress
Project description:The current project is within the range of molecular immunogenetic auto immune diseases and refers to the comparative study of promiscuous gene expression of tissue-specific antigens (TSAs) in the thymus of NOD mice line (non obese diabetic) who plays the auto-immune diabetes mellitus type 1, during the transition from state pre-diabetics to diabetics. Use the technology of oligo arrays to investigate the expression of miRNAs and cDNA microarrays to investigate the expression of genes encoding the messenger RNAs including TSAs (tissue specific antigens).
2009-10-10 | E-MEXP-2245 | biostudies-arrayexpress