Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47159 | GEO | 2014/08/22
SECONDARY ACCESSION(S): PRJNA204589
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-08-22 | E-GEOD-47159 | biostudies-arrayexpress
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.
2014-08-22 | GSE57112 | GEO
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression at P1 was measured in neonates with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and compared to that of wild-type littermates (n=5). KO_normoglycemic and KO_hypoglycemic individuals correspond to mutant pups wild mild hypoglycemia (n=3) and with severe hypoglycemia (n =7), respectively.
2014-08-22 | E-GEOD-57112 | biostudies-arrayexpress
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.
2014-08-22 | GSE47156 | GEO
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster (KO) and in wild-type littermates (WT) at embryonic day E19.5 (n=3 per genotype) and on the day of birth (P0, n=4 WT and 5 KO).
2014-08-22 | E-GEOD-47156 | biostudies-arrayexpress
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the mother’s milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions.
2014-08-22 | GSE47155 | GEO
Project description:In placental mammals, adaptation to extra-uterine life requires complex metabolic adjustments linked to the abrupt transition from the transplacental transfer of glucose toward the use of fat originating from the motherM-bM-^@M-^Ys milk as a major energy source. The study of a novel knock-out mouse model led us to identify the biological roles of the miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 cluster is the largest mammalian-specific miRNA cluster composed of 39 pre-miRNA and expressed from the maternally-inherited allele. We unexpectedly found that ~ 35% of heterozygous neonates with a maternal - but not paternal - deletion of the entire 40kb-long miRNA cluster die shortly after birth due to defects in the maintenance of energy homeostasis, as evidenced by impaired hepatic glycogenolysis, gluconeogenesis and ketogenesis. This maladaptive metabolic response is accompanied by profound changes in the neonatal hepatic gene expression program, notably a decrease in the activation of a large set of metabolic genes linked to lipid metabolism. Our study unveils essential roles for the miR-379/miR-410 cluster at the transition from fetal to postnatal life, revealing new layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on postnatal metabolic functions. Liver gene expression was measured in mice with a maternally-inherited deletion of the miR-379/miR-410 cluster and in wild-type littermates at embryonic day E19.5, 4h following the caesarean delivery (n=4 biological replicates per genotype)
2014-08-22 | E-GEOD-47155 | biostudies-arrayexpress
Project description:Hepatic transcriptome of mice with a deletion of the miR-379/miR-410 cluster
| PRJNA204589 | ENA
Project description:In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR-379/miR-410 cluster within the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 locus, also named C14MC in humans, is the largest known placental mammal-specific miRNA cluster, whose 39 miRNA genes are expressed only from the maternal allele. We found that heterozygote pups with a maternal--but not paternal--deletion of the miRNA cluster display partially penetrant neonatal lethality with defects in the maintenance of energy homeostasis. This maladaptive metabolic response is caused, at least in part, by profound changes in the activation of the neonatal hepatic gene expression program, pointing to as yet unidentified regulatory pathways that govern this crucial metabolic transition in the newborn's liver. Not only does our study highlight the physiological importance of miRNA genes that recently evolved in placental mammal lineages but it also unveils additional layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on metabolic control at birth and have likely contributed to mammal evolution.
| S-EPMC4282508 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Emerging evidence suggests that microRNAs (miRNAs) are essential for the metabolic homeostasis of liver tissues. Many hepatic miRNAs located in the miR-379/miR-544 cluster were significantly increased in leptin-receptor-deficient type 2 mice (db/db), a mouse model of diabetes. However, the function of the miR-379/miR-544 cluster in the process of hepatic steatosis remains unclear. Here, we report that the novel function of miR-379/miR-544 cluster in regulating obesity-mediated metabolic dysfunction. Genetical mutation of miR-379/miR-544 cluster in mice displayed resistance to high-fat diet (HFD)-induced obesity with moderate hepatic steatosis and hypertriglyceridemia. In vitro studies revealed that silencing of miR-379 in human hepatocellular carcinoma (HepG2) cells ameliorated palmitic acid-induced elevation of cellular triglycerides, and overexpression of miR-379 had the opposite effect. Moreover, Igf1r (Insulin-like growth factor 1 receptor) and Dlk1 (Delta-like homolog 1) were directly targeted by miR-379 and miR-329, respectively, and elevated in the livers of the miR-379/miR-544 cluster knockout mice fed on HFD. Further transcriptome analyses revealed that the hepatic gene expressions are dysregulated in miR-379/miR-544 knockout mice fed with HFD. Collectively, our findings identify the miR-379/miR-544 cluster as integral components of a regulatory circuit that functions under conditions of metabolic stress to control hepatic steatosis. Thus, this miRNA cluster provides potential targets for pharmacologic intervention in obesity and NAFLD.
| S-EPMC8435714 | biostudies-literature