HeLa cell: DUSP2 overexpression vs. control
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66656 | GEO | 2015/09/30
SECONDARY ACCESSION(S): PRJNA277631
REPOSITORIES: GEO
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Project description:To study the gene expression profile in the mesendoderm differerntiation of control and Hif-1a overexpression, we performed RNA-seq on the total RNA samples collected from the differentiation of control and Hif-1a overexpression AB2.2 mESCs at differentiation day 4.In addition, to study the gene expression profile in the mesendoderm differerntiation of Hif-1a knockdown under normoxia and hypoxia, we performed RNA-seq on the total RNA samples collected from the differentiation of Hif-1a knockdown AB2.2 mESCs under normoxia or hypoxia at differentiation day 4. Cell lines were built by infecting AB2.2 cells with lentiviruses. Each group contained three biological replicates. The expression matrix was obtained by Hisat2 followed by Stringtie.
2022-09-27 | GSE208062 | GEO
Project description:Recently, hypoxia via the transcription factor HIF-1a has been implicated to play an important role for the fate of the adaptive immune response by regulatory T cells (Treg) and T helper 17 cells (TH17) in the mouse model. However, the reports on the effect of HIF-1a are conflicting and so far no functional data in the human system are available. Therefore, we analyzed the effect of hypoxia and HIF-1a on Treg and TH17 in the human system. FACS, western blot and reporter assays clearly demonstrated that hypoxia does not up-regulate the level of HIF-1a in CD4+ T cells (THC) and microarray analysis revealed no change of the transcriptome comparing normoxia vs. hypoxia. Furthermore, we could show that HIF-1a is almost exclusively regulated via NF-kB and NFAT, whereas hydroxylation and subsequent degradation of HIF-1a had little to no effect. In addition, we showed that HIF-1a is essential for nTreg mediated suppression and for IL-17A secretion of TH17, but not for TH17 lineage commitment measured by RORγt expression. In conclusion, our results demonstrated that THC have a distinct regulation of HIF-1a protein levels, which was absolutely essential for Treg and TH17 function.
2013-12-31 | GSE41999 | GEO
Project description:HIF-1a and HIF-2a are expressed at high levels in mesenchymal progenitors compared to more committed mesenchymal cells and hematopoietic cells. HIF-factors could therefore have a role in the regulation the biology of mesenchymal progenitors and their functions, like the non cell-autonomous maintenance of hematopoietic progenitors. We used microarrays to detail the global program of gene expression regulated by HIF-1a or HIF-2a in mesenchymal progenitors Mesenchymal progenitors were FACS-sorted and cultured in low oxygen concentration for few days. Once cells started to form CFU-F colonies, we transduced them with shRNAs targeting specifically HIF-1a or HIF-2a. Four days after transduction, cells were collected and RNA extracted for microarray analysis.
2014-03-25 | E-GEOD-56141 | biostudies-arrayexpress
Project description:Recently, hypoxia via the transcription factor HIF-1a has been implicated to play an important role for the fate of the adaptive immune response by regulatory T cells (Treg) and T helper 17 cells (TH17) in the mouse model. However, the reports on the effect of HIF-1a are conflicting and so far no functional data in the human system are available. Therefore, we analyzed the effect of hypoxia and HIF-1a on Treg and TH17 in the human system. FACS, western blot and reporter assays clearly demonstrated that hypoxia does not up-regulate the level of HIF-1a in CD4+ T cells (THC) and microarray analysis revealed no change of the transcriptome comparing normoxia vs. hypoxia. Furthermore, we could show that HIF-1a is almost exclusively regulated via NF-kB and NFAT, whereas hydroxylation and subsequent degradation of HIF-1a had little to no effect. In addition, we showed that HIF-1a is essential for nTreg mediated suppression and for IL-17A secretion of TH17, but not for TH17 lineage commitment measured by RORγt expression. In conclusion, our results demonstrated that THC have a distinct regulation of HIF-1a protein levels, which was absolutely essential for Treg and TH17 function. 3 patients, 2 cell type, 2 treatments = 12 arrays
2013-12-31 | E-GEOD-41999 | biostudies-arrayexpress
Project description:<p>Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining <em>in situ</em> metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1a as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+) levels. The HIF-1a/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steadystate conditions. In contrast, in activated NK cells under hypoxia, HIF-1a is required for glycolysis, and forced HIF-1a expression boosts glycolysis and NK cell performance <em>in vitro</em> and <em>in vivo</em>. Our data highlight two distinct pathways by which HIF-1a interferes with NK cell metabolism. While HIF-1a-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1a-dependent tryptophan/NAD+ metabolism.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>RNA-seq data associated with this study are available in ArrayExpress (BioStudies): accession <a href='https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-12082' rel='noopener noreferrer' target='_blank'>E-MTAB-12082</a>.</p>
2023-06-01 | MTBLS6863 | MetaboLights
Project description:HIF-1a activates genes under hypoxia and was hypothesized to regulate bone regeneration. Surprisingly, HET HIF-1a fracture calluses are larger, stronger and stiffer than WT HIF-1a calluses due to decreased apoptosis. These data identify apoptosis inhibition as a means to enhance bone regeneration. Introduction: Bone regeneration subsequent to fracture involves the synergistic activation of multiple signaling pathways. Localized hypoxia following fracture activates hypoxia-inducible factor 1 alpha (HIF-1a) leading to increased expression of HIF-1 target genes. We therefore hypothesized that HIF-1a is a key regulator of bone regeneration Materials and Methods: Fixed femoral fractures were generated in mice with partial HIF-1a deficiency (HET HIF-1a) and wild type littermates (WT HIF-1a). Fracture calluses and intact contralateral femurs from post fracture day (PFD) 21 and 28 (N=5-10) were subjected to MicroCT evaluation and 4-point bending in order to assess morphometric and mechanical properties. Molecular analyses were carried out on PFD 7, 10 and 14 samples (N=3) to determine differential gene expression at both mRNA and protein levels. Finally, TUNEL staining was performed on PFD 14 samples (N=2) to elucidate differential apoptosis. Results: Surprisingly, fracture calluses from HET HIF-1a mice exhibit greater mineralization and are larger, stronger and stiffer. Microarray analyses focused on hypoxia-induced genes revealed differential expression (between genotypes) of several genes associated with the apoptotic pathway. Real-time PCR confirmed these results, demonstrating higher expression of pro-apoptotic PP2A and lower expression of anti-apoptotic BCL2 in WT HIF-1a calluses. Subsequent TUNEL staining demonstrates that WT HIF-1a calluses contain larger numbers of TUNEL positive chondrocytes and osteoblasts than HET HIF-1a calluses. Conclusions: We conclude that partial HIF-1a deficiency results in decreased chondrocytic and osteoblastic apoptosis; thereby allowing the development of larger, stiffer calluses and enhancing bone regeneration. Furthermore, apoptosis inhibition may be a promising target for developing new treatments to accelerate bone regeneration. Keywords: Bone, Fracture, Apoptosis, Hypoxia, Microarray
2007-01-12 | GSE6091 | GEO
Project description:HIF-1a and HIF-2a are expressed at high levels in mesenchymal progenitors compared to more committed mesenchymal cells and hematopoietic cells. HIF-factors could therefore have a role in the regulation the biology of mesenchymal progenitors and their functions, like the non cell-autonomous maintenance of hematopoietic progenitors. We used microarrays to detail the global program of gene expression regulated by HIF-1a or HIF-2a in mesenchymal progenitors
2014-03-25 | GSE56141 | GEO
Project description:In the related study, to determine whether DUSP2 definitively served as a phosphatase for STAT3, an in vitro phosphatase assay was used. Using S-tag beads, p-STAT3 was pulled down from IL-6 stimulated HEK293T cells transfected with STAT3-S-Tag. DUSP2 or control protein, which was purified from HEK293T cells transfected with DUSP2-FLAG or empty vector through extraction with anti-FLAG beads and elution with FLAG peptides, were incubated with p-STAT3-S-Tag-beads in phosphatase buffer. Then bound proteins were eluted and subjected to MS analysis. When compared with the control, incubation of STAT3 and DUSP2 led to dephosphorylation of two STAT3 residues that have been reported to promote its activity, namely tyrosine 705 and serine 727.
2015-10-13 | PXD002743 | Pride
Project description:Neuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors.
2010-07-13 | GSE18478 | GEO
Project description:Neuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors. 12 prostate tumor samples were analyzed during normoxia and hypoxia, with different FOX/HIF genotypes. The pivotal samples are represented as duplicates.
2010-07-13 | E-GEOD-18478 | biostudies-arrayexpress