PGC1beta is a transcriptional coactivator that potently stimulates mitochondrial biogenesis and respiration of cells. Here, we have generated mice lacking exons 3 to 4 of the Pgc1beta gene (PGC1beta E3,4-/E3,4- mice). These mice express a mutant protein that has reduced coactivation activity on a subset of transcription factors, including ERRalpha, a major target of PGC1beta in the induction of mitochondrial gene expression. The mutant mice have reduced expression of OXPHOS genes and mitochondrial dysfunction in liver and skeletal muscle as well as elevated liver triglycerides. Euglycemic-hyperinsulinemic clamp and insulin signaling studies show that PGC1beta mutant mice have normal skeletal muscle response to insulin, but have hepatic insulin resistance. These results demonstrate that PGC1beta is required for normal expression of OXPHOS genes and mitochondrial function in liver and skeletal muscle. Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver.
Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance.
No sample metadata fields
View SamplesWe compared the transcriptional profile of mammary tumors spontaneously developed in PyMT transgenic mice either bearing or not additional copies of the endogeneous SIRT6 gene.
SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity.
Sex, Age, Specimen part
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesHuman myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
No sample metadata fields
View SamplesDrought is an important environmental factor affecting plant growth and biomass production. Despite this importance little is known on the molecular mechanisms regulating plant growth under water limiting conditions. The main goal of this work was to investigate, using a combination of growth and molecular profiling techniques, how stress arrests CELl proliferation in Arabidopsis thaliana leaves upon osmotic stress imposition.
Pause-and-stop: the effects of osmotic stress on cell proliferation during early leaf development in Arabidopsis and a role for ethylene signaling in cell cycle arrest.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Inactivating hepatic follistatin alleviates hyperglycemia.
Sex, Specimen part
View SamplesWe compared RNA expression profiles of wild type of mice maintained on high fat diet or Irs1/2:foxo1-LTKO mice infected with Fst288 AAV-TBG virus
Inactivating hepatic follistatin alleviates hyperglycemia.
Sex, Specimen part
View SamplesWe compared RNA expression profiles of eWAT obtained from Cntr- and LDKO-mice, and Cntr3- and LTKO-mice.
Inactivating hepatic follistatin alleviates hyperglycemia.
Sex, Specimen part
View SamplesDiet-induced obesity is characterized by macrophage (MF) infiltration and low-grade chronic inflammation in white adipose tissue (WAT) leading to insulin resistance. WAT MF are highly heterogeneous in their origin, patterns of gene expression and activities: unlike infiltrating monocyte-derived MF that promote inflammation and metabolic dysfunction, tissue-resident WAT MF originally described as ‘M2’ are phenotypically anti-inflammatory and counteract obesity and insulin resistance. Despite the critical role of the balance between these MF populations in metabolic homeostasis, the molecular mechanisms and key players that establish the resident MF transcription program are poorly understood. We recently reported that glucocorticoid receptor (GR)-interacting protein (GRIP)1 - a nuclear receptor coactivator - cooperates with GR to repress transcription of inflammatory genes. Here, using mice conditionally lacking GRIP1 in MF (cKO), we show that GRIP1 promotes MF polarization in response to IL4 (M2(IL4)) via a nuclear receptor-independent pathway by serving as a coactivator for Kruppel-like factor (KLF)4 – a critical driver of tissue MF differentiation. Interestingly, in vivo, GRIP1 cKO mice challenged with high-fat diet develop massive MF infiltration and chronic inflammation in WAT and liver, fatty livers, hyperglycemia, hyperinsulinemia and glucose intolerance consistent with metabolic syndrome phenotype. Together, our findings identify GRIP1 as a critical regulator of immunometabolism, which relies on distinct transcriptional mechanisms to coordinate the balance between MF populations in vivo thereby protecting mice from obesity-induced metabolic disease. Overall design: 1. Examination of IL4 induced transcriptome in in vitro differentiated primary bone marrow-derived macrophages. 2. Examination of macrophage transcriptome in macrophages isolated from the white adipose tissue of the WT and GRIP1(cKO) conditional KO animals
The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis.
Sex, Age, Specimen part, Subject
View SamplesGermline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. Overall design: RNA-sequencing of 12 Smarcb1-deficient mouse cranial nerves and meninges tumors
Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.
Specimen part, Subject
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