Gene-by-sex interactions in mitochondrial functions and tissue-specific gene expression in cardio-metabolic traits
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA449550 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6979440_1.fastq.gz | Fastqsanger.gz | |||
| SRR6979440_2.fastq.gz | Fastqsanger.gz | |||
| SRR6979450_1.fastq.gz | Fastqsanger.gz | |||
| SRR6979450_2.fastq.gz | Fastqsanger.gz | |||
| SRR6979470_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 128 |
Similar Datasets
Project description:We report a multi-omic study of sex differences and gene-by-sex interactions across a panel of 100 inbred strains of mice (the Hybrid Mouse Diversity Panel, HMDP), with a focus on metabolic and cardiovascular traits. For all traits examined, including obesity, insulin resistance, fatty liver, atherosclerosis, and gut microbiota composition, sex differences were influenced by genetic background. Loci identified by genome-wide association studies (GWAS) of the traits were frequently influenced by sex. Lyplal1, a gene implicated in human obesity, was shown to underlie a sex-specific locus for diet induced obesity. Many of the sex-dependent traits showed interdependencies as judged by correlation and shared gene expression patterns, indicating higher order regulation. Global gene expression analyses of tissues across the HMDP indicated that sex differences in mitochondrial functions in adipose contributed to many of the traits. Consistent with this, we observed that females tended to be more resistant to the adverse effects of a high fat diet, with smaller adipocytes and increased “browning” of white adipose tissue as compared to males. Sex-specific differences in mitochondrial activity were confirmed by examining respiration of isolated mitochondria. Gonadectomy experiments revealed thousands of genes influenced by sex hormones. In liver, a tissue exhibiting particularly strong differences in gene expression between tissues, sex hormones appeared to be the primary driver of the differences, whereas in adipose organizational effects of sex appeared to be more important.
2018-04-10 | GSE112947 | GEO
Project description:We studied sex differences in over 50 cardio-metabolic traits in a panel of 100 diverse inbred strains of mice. The results clearly showed that the effects of sex on both clinical phenotypes and gene expression depend on the genetic background. In support of this, genetic loci associated with the traits frequently showed sex specificity. For example, Lyplal1, a gene implicated in human obesity, was shown to underlie a sex-specific locus for diet-induced obesity. Global gene expression analyses of tissues across the panel implicated adipose tissue "beiging" and mitochondrial functions in the sex differences. Isolated mitochondria showed gene-by-sex interactions in oxidative functions, such that some strains (C57BL/6J) showed similar function between sexes, whereas others (DBA/2J and A/J) showed increased function in females. Reduced adipose mitochondrial function in males as compared to females was associated with increased susceptibility to obesity and insulin resistance. Gonadectomy studies indicated that gonadal hormones acting in a tissue-specific manner were responsible in part for the sex differences.
| S-EPMC6447452 | biostudies-literature
Project description:Inappropriate or sustained activation of innate immunity is a pathologic feature of several common cardio-metabolic disorders. Little is known, however, about transcriptomic modulation during inflammatory stress in disease-relevant human tissues. We applied deep RNA sequencing (RNA-seq) during low-dose experimental endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner, inflammatory tissue-level transcriptome responses of relevance to complex cardio-metabolic diseases. We utilized adipose and blood samples from three individuals who underwent a standardized inpatient endotoxemia protocol. Our comprehensive analysis revealed substantial, highly tissue- and subject-specific LPS-modulated changes in the expression of protein-coding genes and linc-RNAs as well as alternative splicing (AS). We also confirmed adipocytes and macrophages as potential cell sources of selective LPS-modulated linc-RNAs and AS events. Finally, we defined disease relevance of a subset of findings in obese adipose tissue and through interrogation of overlap with genome-wide association study loci for cardio-metabolic traits. Our findings provide novel insights into tissue-level genomic regulation, not detectable through analysis of DNA variations alone, of relevance to common cardio-metabolic diseases. Using RNA-seq data to study LPS-modulated changes in lincRNA expression for adipose and blood of a healthy individual.
2014-01-02 | E-GEOD-50792 | biostudies-arrayexpress
Project description:Inappropriate or sustained activation of innate immunity is a pathologic feature of several common cardio-metabolic disorders. Little is known, however, about transcriptomic modulation during inflammatory stress in disease-relevant human tissues. We applied deep RNA sequencing (RNA-seq) during low-dose experimental endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner, inflammatory tissue-level transcriptome responses of relevance to complex cardio-metabolic diseases. We utilized adipose and blood samples from three individuals who underwent a standardized inpatient endotoxemia protocol. Our comprehensive analysis revealed substantial, highly tissue- and subject-specific LPS-modulated changes in the expression of protein-coding genes and linc-RNAs as well as alternative splicing (AS). We also confirmed adipocytes and macrophages as potential cell sources of selective LPS-modulated linc-RNAs and AS events. Finally, we defined disease relevance of a subset of findings in obese adipose tissue and through interrogation of overlap with genome-wide association study loci for cardio-metabolic traits. Our findings provide novel insights into tissue-level genomic regulation, not detectable through analysis of DNA variations alone, of relevance to common cardio-metabolic diseases.
2014-01-02 | GSE50792 | GEO
Project description:Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs.
2009-07-23 | GSE15214 | GEO
Project description:The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy. Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice.
2012-03-19 | GSE36591 | GEO
Project description:Oculo-facio-cardio-dental syndrome (OFCD) is a rare genetic disorder characterized by teeth with extremely long roots (radiculomegaly), and craniofacial, eye and cardiac abnormalities. The mutation of the transcriptional co-repressor BCOR has been identified as being responsible for oculo-facio-cardio-dental (OFCD) syndrome. Mesenchymal stem cells (MSCs) is isolated from the root apical papilla of an OFCD patient. Gene expression profiling is performed and compared between mutant MSCs and wild type MSCs. Total RNA were extracted from normal MSCs (MSCWT) and mutant MSCs (MSCO).
2009-07-23 | E-GEOD-15214 | biostudies-arrayexpress
Project description:The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy. Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice. We conducted abdominal aorta banding or sham operation at 0 week, then We conducted uninephrectomy or sham operation at 2 week. We removed these kidney 6week after the uninephrectomy. These RNA samples were purified from the homogenized kidneys.
2012-03-19 | E-GEOD-36591 | biostudies-arrayexpress
Project description:Background: Despite endothelial dysfunction being considered as the initial step of the development of hypertension and associated cardio-renal syndromes, effective therapeutic strategies to prevent endothelial injuries are still lacking. GPR183 is a recently identified GPCR for oxysterols and hydroxylated metabolites of cholesterol. Here, we explored a previously unappreciated role of GPR183 in hypertension and age-related cardio-renal injuries. Methods and results: Mice were treated with DOCA/Salt or AngII to induce hypertension. we found that endothelial GPR183 was significantly induced in aged or hypertensive mice, which was further confirmed in renal biopsies from elderly people or subjects with hypertensive nephropathy. In addition, we found that endothelial-specific GPR183 deletion markedly ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Mechanistically, we found that GPR183 disrupted circadian signaling by inhibiting PER1 expression, thereby facilitating endothelial senescence and dysfunction through the cAMP/PKA/CREB signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or Clotrimazole ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Conclusions: GPR183 is an attractive therapeutic target for hypertension and age-related diseases. Targeting GPR183 could provide novel strategies for managing hypertension and its associated cardio-renal injuries.
2024-06-23 | GSE270175 | GEO
Project description:Liver, Fat, Kidney and Muscle Gene Expression Profiles in a Rat Congenic Strain of the Cardio-Metabolic Syndrome
2008-07-04 | E-MEXP-1695 | biostudies-arrayexpress