For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the 'alarmin' IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein, and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. Overall design: mRNA profiles of brown adipose tissues and inguinal white adipose tissues from postnatal day 0.5 and 24, respectively, WT and IL-33 knockout mice.
Perinatal Licensing of Thermogenesis by IL-33 and ST2.
Specimen part, Subject
View SamplesHomozygous disruption of Bteb2/Klf5, a homolog of Drosophila gap gene Krppel, led to increased expression of various differentiation marker genes, such as Fgf5, Cdx2, and Brachyury in mouse ES cells without compromising their ability to differentiate into all three germ layers. Upon removal of LIF, Klf5-deficient ES cells showed faster differentiation kinetics than wild-type ES cells. In contrast, overexpression of Klf5 in ES cells suppressed the transcription of differentiation marker genes, and maintained pluripotency in the absence of LIF. In order to search downstream genes of Klf5, we surveyed genes implicated in ES cell proliferation by microarray analysis
Krüppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs.
No sample metadata fields
View SamplesEmbryos were collected, aged, mock-treated/treated with 40Gy gamma radiation, and allowed to recover for 1.5 hours. Targets from 3 sets of wild type (yw, w1118) and 2 sets of mutant (Dmp53NS) biological replicates were generated and the expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with radiation-responsive and Dmp53-dependent expression patterns.
p53 directs focused genomic responses in Drosophila.
No sample metadata fields
View SamplesKc167 cells were mock-treated/treated with combinations of steroid hormone ecdysone and gamma-irradiation, and harvested. The expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with ecdysone- and/or radiation-responsive expression patterns.
p53 directs focused genomic responses in Drosophila.
No sample metadata fields
View SamplesWhite Striping and Wooden Breast (WS/WB) are abnormalities increasingly occurring in the fillets of high breast yield and growth rate chicken hybrids. These defects lead to consistent economic losses for poultry meat industry, as affected broilers fillets present an impaired visual appearance that negatively affects consumers acceptability. Previous studies have highlighted in affected fillets a deeply damaged muscle, showing profound inflammation, fibrosis and lipidosis. The present study investigated the differentially expressed genes and pathways linked to the compositional changes observed in WS/WB breast muscles, in order to outline a more complete framework of the gene networks related to the occurrence of this complex pathological picture. The biochemical composition was performed on 20 Pectoralis major samples obtained from high breast yield and growth rate broilers (10 affected vs. 10 normal) and 12 out of the 20 samples were used for the microarray gene expression profiling (6 affected vs. 6 normal). The obtained results indicate strong changes in muscle mineral composition, coupled to an increased deposition of fat. In addition, 204 differentially expressed genes (DEG) were found: 102 up-regulated and 102 down-regulated in affected breasts. The gene expression pathways found more altered in WS/WB muscles are those related to muscle development, polysaccharide metabolic processes, proteoglycans synthesis, inflammation and calcium signaling pathway. On the whole, the findings suggest that a multifactorial and complex etiology is associated with the occurrence of WS/WB muscle abnormalities, contributing to further define the transcription patterns associated to these myopathies.
Detection of differentially expressed genes in broiler pectoralis major muscle affected by White Striping - Wooden Breast myopathies.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Specimen part
View SamplesMutations in IDH1 and IDH2 are frequently observed in various cancers, including acute myeloid leukemia (AML). Mutant IDHs convert -ketoglutarate (-KG) to 2-hydroxyglutarate (2-HG), which dysregulates a set of-KG-dependent dioxygenases. To determine whether mutant IDHs are valid targets for cancer therapy, we established a mouse AML model harboring an IDH2 mutation by transplanting mice with nucleophosmin1 (NPM1)+/- mouse hematopoietic stem/progenitor cells that had been co-transduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H and FLT3/ITD) that frequently occur simultaneously in human AML patients. IDH2/R140Q is necessary for the engraftment or survival of NPMc+ cells in vivo.Gene-expression analysis indicated that NPMc increased the expression of Hoxa9, and that IDH2/R140Q increased the level of Meis1 and activated the hypoxia pathway in AML cells.Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q reversibly decreased the levels of 5hmC modification and gene expression at some differentiation inducing genes (Ebf1, Pax5 and Spib). These results indicate that the IDH2 mutation is critical for the development and maintenance of AML stem cells, and that mutant IDHs are promising targets for anticancer therapy.
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Specimen part
View SamplesThe SSG1-1 mutation was an allele of the YHR032W gene in Saccharomyces cerevisiae. The SSG1-1 mutants contained higher levels of AdoMet than wild type (WT). SSG1-1 single mutants were shown to have a long lifespan, suggesting that the Ssg1-1 protein might have a role in longevity.
Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK.
No sample metadata fields
View SamplesGene expression study of human and Chimpanzee iPS cell.
New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood.
Specimen part
View SamplesThe liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase C?-mediated NF-?B activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca2+ levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver stage development of the P. berghei rodent malaria parasite and the human P. falciparum parasite also. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis. Overall design: To explore the molecular mechanisms by which the HGF/MET/PKC?/NF-?B pathway regulates P. berghei sporozoite development in hepatocytes, we compared the gene expression patterns in wild-type and PKC?-KO Huh7 cells treated or not treated with HGF. We also analyzed the gene expression profiles in wild type and PKC?-KO Huh7 cells uninfected or infected with P. berghei sporozoites.
CXCR4 regulates <i>Plasmodium</i> development in mouse and human hepatocytes.
Specimen part, Subject
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