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

Identification of hypoxia regulated HIF-1A and HIF-2A specific target genes in Glioblastoma

Project description:HIF-1A and HIF-2A regulate both overlapping and unique target genes in response to hypoxia. In this dataset, we identify specific HIF-1A and HIF-2A target genes in glioblastoma cells. 12 samples were analysed comprising 4 experimental conditions (normoxia scr, hypoxia scr, hypoxia siHIF1, hypoxia siHIF2) in triplicate. We made pairwise comparisons between the averages of each triplicate set to normoxia scr using the Partek suite.

2012-02-25 | E-GEOD-27523 | biostudies-arrayexpress

Expression data from Mesenchymal progenitor cells knocked down for HIF-1a or HIF-2a expression

2014-03-25 | GSE56141 | GEO

HIF-1a and HIF-2a differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

Project description:Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1alpha and HIF-2a transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1a as an inhibitor and HIF-2a as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1a and HIF-2a are required for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1alpha regulates glycolysis while HIF-2a regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2a-deficient tumours were characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlated with altered immune microenvironment in human ccRCC. These studies reveal an oncogenic role of HIF-1alpha in ccRCC initiation and suggest that alterations in the balance of HIF-1alpha and HIF-2a activities can affect different aspects of ccRCC biology and disease aggressiveness.

2020-05-22 | GSE150983 | GEO

Transcription profiling of liver from mice with constitutively active Hypoxia Inducible Factor (HIF-1a and HIF-2a) or inactivated von Hippel-Lindau tumor suppressor gene product (pVHL)

Project description:The effects of constitutively active Hypoxia Inducible Factor (HIF) and inactivated von Hippel-Lindau tumor suppressor gene product (pVHL) were examined in a mouse model. Conditionally expressed, constitutively active HIF-1a and HIF-2a were compared with inactivated pVHL.

2006-09-21 | E-MEXP-856 | biostudies-arrayexpress

Influences of chronic hypoxia and hypoxic-inducible factor 2A on mouse myoblasts

Project description:The extracellular oxygen levels play a crucial role in the control of cellular metabolism and behaviors under various physiological and pathological conditions. When mammalian cells sense insufficient oxygen levels, one of the most important responses is to stabilize hypoxic-inducible factors. While the functions of HIF-1A and acute hypoxia signaling have been extensively studied in many cell types, the impacts of HIF-2A and chronic hypoxia on skeletal muscle myoblasts have not been fully understood.

2024-04-17 | GSE243799 | GEO

Citrullination modulation maintains HIF-1A stabilization to drive tumor progression

Project description:HIF-1 (Hypoxia-inducible factor 1) is the master regulator responding to hypoxic conditions. Here, we found that HIF-1A is citrullinated by peptidyl arginine deiminase 4 (PADI4) at arginine 698, promoting HIF-1A stabilization and thus HIF-1-driven tumor growth. The knockdown of PADI4 could dramatically decrease HIF-1 protein expression without affecting the mRNA level, and this could be rescued by the proteasome inhibitor MG132 treatment under hypoxia. And PADI4-HIF-1A interaction is critical for HIF-1A stability and tumor progression, depending on the enzymatic activity of PADI4 and the pocket structure of PADI4. DHE, an FDA-approved agent for the treatment of migraine, was found serve as a potential antitumor agent throgh disrupting PADI4-HIF-1A interaction and suppressing HIF-1A stability. Taken together, we found the anti-tumor effect of DHE due to its effect on blocking PADI4-HIF-1A interaction and downregulating HIF-1A pathway in cancer cells. To figure out the influence of DHE on liver cancer cell under hypoxia, we treated Hep3B cell lines with two does DHE in 6 hours under Hypoxia and extracted mRNA for furthur RNA seq.

2024-05-28 | GSE233772 | GEO

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