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
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.
Project description:Differential expression of the oxygen sensitive hypoxia-inducible transcription factor (HIF) subunits HIF-1a and HIF-2a occurs in many tumor types, but the underlying regulatory mechanisms remain poorly understood. Here we investigate the role of mTOR complex in the regulation of HIF expression in cells cultured under hypoxic conditions.
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.
Project description:Differential profiles from whole genome human expression arrays on monocytes obtained from peripheral blood in COPD was studied and compared with controls. Monocytes were isolated from Controls (Group 1) which included Control Smokers (Group 1A) and Control Never Smokers (Group 1B) and COPD (Group 2) which included COPD Smokers (Group 2A) and COPD ExSmokers (Group 2B). Differential transcriptomic expression associated with (i) Smoking, (ii) COPD, and (iii) cessation of smoking were identified.
Project description:General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumour suppressor. However HIF-1a and HIF-2a have contrasting effects on experimental tumour progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1a and HIF-2a and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1a-specific binding, and genes associated with favourable prognosis and between HIF-2a-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-a isoform contributes a highly complex mix of pro- and anti-tumorigenic effects ChIP and RNASeq of HIF-1a and HIF-2a transfection in 786-O cell lines
Project description:Differential expression of the oxygen sensitive hypoxia-inducible transcription factor (HIF) subunits HIF-1a and HIF-2a occurs in many tumor types, but the underlying regulatory mechanisms remain poorly understood. Here we investigate the role of mTOR complex in the regulation of HIF expression in cells cultured under hypoxic conditions. Neuroblastoma SK-N-BE(2)c cells were treated with DMSO or the mTORC complex inhibitor PP242 and cultured at hypoxia for 24, 48 or 72 hours.
Project description:General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumour suppressor. However HIF-1a and HIF-2a have contrasting effects on experimental tumour progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1a and HIF-2a and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1a-specific binding, and genes associated with favourable prognosis and between HIF-2a-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-a isoform contributes a highly complex mix of pro- and anti-tumorigenic effects
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.
