Adipose tissue Glut4 overexpression or knockout
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Mark Herman
PROVIDER: E-GEOD-35378 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Mutation or epigenetic silencing of the transcription factor C/EBP? is observed in ~10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but down-stream targets relevant for leukemogenesis are not known. Here we identify Sox4 as a direct target of C/EBP? whereby its expression is inversely correlated with C/EBP? activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia initiating cells (LICs) from both Sox4 overexpression and murine mutant C/EBP? AML models clustered together, but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP? inactivation contributes to the development of leukemias with a distinct LIC phenotype. K/L (bi-allelic Cebpa mutations) leukemic mice and Sox4 overexprssing leukemic mice were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the C57/BL6 wild type mice.
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2011-12-01 | E-GEOD-33031 | biostudies-arrayexpress
Project description:In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver hematopoietic stem cells (HSCs). However, its function in adult HSCs is unknown. Here, using an inducible knockout model, we found that C/EBPa deficient adult HSCs underwent a pronounced expansion with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover we observed that age-specific C/EBPa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically, we identified N-Myc as a C/EBPa downstream target. C/EBPa upregulation during HSC transition from an active fetal state to a quiescent adult state was accompanied by down-regulation of N-Myc, and loss of C/EBPa resulted in de-repression of NMyc. Our data establish that C/EBPa acts as a molecular switch between fetal and adult states of HSC in part via transcriptional repression of the proto-oncogene N-Myc. HSCs of Pu.1 knock-in (PU.1ki/ki) mice were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the corresponding wild type.
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2015-05-21 | E-GEOD-64052 | biostudies-arrayexpress
Project description:In order to address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC), transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumors was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC. We used the following tissue samples to obtain transcriptional profiling of kidney tumors using Affymetrix HGU-133A chips: 23 Normal, 32 clear cell RCC (cRCC), 11 papillary RCC (pRCC), 6 chromophobe RCC (chrRCC), 12 Oncocytoma (OC), and 8 transitional cell carcinoma (TCC). The supplementary file 'GSE15641_mas5_data.txt' contains MAS5 signal values for the Samples included in Series GSE15641. This dataset is part of the TransQST collection.
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