Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1 in the adaptive response, however, has not been determined. Here we investigate how HIF-1 influences hypoxic adaptation throughout Drosophila development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in dHIF mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIF and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIF in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs.
HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster.
Specimen part
View SamplesCancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Specimen part
View SamplesWT-1 is a zinc-finger transcription factor with important roles during development. WT-1 is associated with the development of tumors of varied origins.
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Cell line, Treatment
View SamplesThis study aimed at characterizing the effect of the innate immune agonist, dsRNA, on ovarian cancer cell lines and ascites-derived ovarian cancer cells.
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Cell line
View SamplesStudies investigating the role of mesenchymal stem cells (MSCs) in mammary carcinogenesis have almost exclusively relied on isolates from bone marrow aspirates or non-breast fat sources often making the general assumption that all MSCs are alike.
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Sex, Specimen part
View Sampleswe aimed to explore the potential therapeutic effects of human mesenchymal stem cell on severe liver disease
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Sex, Specimen part, Cell line
View SamplesAnalyze of RNA expression of Old Fibroblast and Young Fibroblast. Compare RNA expression of Old Fibroblast to RNA expression of Young Fbroblast
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Sex, Specimen part
View Sampleswe analysis of sham fibroblast and UVA fibroblast RNA expression using RNA sequencing and compare RNA expression.
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Sex, Specimen part
View SamplesWe generate miR-25 KO mice by Cas-9 technology, and run 5 month kidney RNA sequencing.
No associated publication
Sex, Specimen part, Cell line
View SamplesAdult neural stem cells derived from wild type and Sirt1 conditional knockout mice were treated with or without X-ray, the total RNA extracted from these cells were used for RNA sequencing.
No associated publication
Sex, Age, Specimen part, Cell line
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