It remains unclear how the ectopic expression of defined transcription factors induces dynamic changes in gene expression profiles that establish a pluripotent state during direct cell reprogramming. In the present study, we first identified a temporal gene expression program during the reprogramming process. Promoter analyses then predicted the role of two forkhead box transcription factors, Foxd1 and Foxo1, as mediators of the gene expression program. Knockdown of Foxd1 or Foxo1 reduced the number of induced pluripotent stem cells (iPSCs). The knockout of Foxd1 prevented the downstream transcription program, including the expression of reprogramming marker genes. Interestingly, the expression level of Foxd1 was also transiently increased in a small population of cells in the middle stage of reprogramming. The presence or absence of Foxd1 expression in this stage was correlated with a future cell fate as iPSCs or non-reprogrammed cells. These results suggest that Foxd1 is a mediator and indicator of the successful progression of the gene expression program in cell reprogramming.
Foxd1 is a mediator and indicator of the cell reprogramming process.
Specimen part, Time
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 SamplesIt remains unclear how the ectopic expression of defined transcription factors induces dynamic changes in gene expression profiles that establish a pluripotent state during direct cell reprogramming. In the present study, we first identified a temporal gene expression program during the reprogramming process. Promoter analyses then predicted the role of two forkhead box transcription factors, Foxd1 and Foxo1, as mediators of the gene expression program. Knockdown of Foxd1 or Foxo1 reduced the number of induced pluripotent stem cells (iPSCs). The knockout of Foxd1 prevented the downstream transcription program, including the expression of reprogramming marker genes. Interestingly, the expression level of Foxd1 was also transiently increased in a small population of cells in the middle stage of reprogramming. The presence or absence of Foxd1 expression in this stage was correlated with a future cell fate as iPSCs or non-reprogrammed cells. These results suggest that Foxd1 is a mediator and indicator of the successful progression of the gene expression program in cell reprogramming.
Foxd1 is a mediator and indicator of the cell reprogramming process.
No sample metadata fields
View SamplesWe report the expression profiles of the nuclear receptor family of transcription factors, known regulators of metabolism, during iPSC generation. Unique but overlapping expression patterns were found in iPSCs derived from adipose derived stem cells (ADSCs) and embryonic fibroblasts (human and mouse) that correlate with developmental transitions in the cell.
ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency.
Specimen part, Cell line, Time
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 SamplesFor 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 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 Samples