Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237310 | ENA |
REPOSITORIES: ENA
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Project description:Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia. CB CD34+ cells were isolated by Miltenyi miniMACS column. Cells were prestimulated in HPGM with 100 ng/ml KITL, FLT3L and TPO for 3 days after which cells were placed either at normoxia or hypoxia (1% O2 for an additional 24 hrs). 5 independent CB CD34+ batches were used and isolated RNA was combined and used for Illumina beadhchip arrays HT12 v4
2014-03-01 | E-GEOD-54661 | biostudies-arrayexpress
Project description:Identification of hypoxia, HIF1 and HIF2 target genes in human CB CD34+ cells
| PRJNA237308 | ENA
Project description:Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia. CB CD34+ cells were isolated by Miltenyi miniMACS column. Cells were prestimulated in HPGM with 100 ng/ml KITL, FLT3L and TPO for 48 hrs. Cells were transduced with control pRRL-IRS2-EGFP lentiviral vectors or vectors expressing HIF1α(P402A,P564A) or HIF2α(P405A,P531A) in one or two rounds of 12 hrs each. 24 hrs later transduced cells were sorted after which RNA was isolated. 5 independent CB CD34+ batches were isolated, transduced and sorted, and isolated RNA was combined and used for Illumina beadhchip arrays HT12 v4
2014-03-01 | E-GEOD-54662 | biostudies-arrayexpress
Project description:Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia.
2014-03-01 | GSE54662 | GEO
Project description:Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia.
2014-03-01 | GSE54661 | GEO
Project description:Identification of hypoxia target genes in human CB CD34+ cells
| PRJNA237311 | ENA
Project description:Hypoxia inducible factors (HIF)1 and 2 are transcription factors which regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in haematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state. Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes like including metabolism, particularly those involved in glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes - but not genes related to the TCA cycle or glutaminolysis - were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34+ cells these loci were predominantly controlled by HIF1 but not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia. These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state.
2020-02-04 | GSE123461 | GEO
Project description:Identification of CITED2 target genes in human CB
| PRJNA205285 | ENA
Project description:Identification of STAT5 target genes in human CB HSC, CMP, GMP and MEP
| PRJNA136285 | ENA
Project description:Acute myeloid leukemia (AML) is characterized by an accumulation of aberrant myeloid cells arrested at different stages of differentiation. Therapeutic approaches that prompt AML blasts to differentiate represent an attractive opportunity in the landscape of AML therapies, as they aim to induce terminal maturation and leukemia debulking without intensive cytotoxic treatments. In the present study, we investigate the involvement of HIF1 and HIF2 transcription factors in AML pathogenesis, and position HIF2 as a novel regulator of the AML differentiation block. We performed a comparative analysis of HIF1 and HIF2 function in AML cell lines via their inhibition with genetic or pharmacological strategies and found that both factors promote AML proliferation and clonogenicity. Importantly, specific inhibition of HIF2 provokes AML cell differentiation in cell lines and patient-derived xenograft (PDX) models. Mechanistically, we found that HIF2 and EZH2, the catalytic subunit of polycomb repressive complex 2, cooperate at favoring EZH2-mediated deposition of the repressive histone mark H3K27me3 on the regulatory regions of myeloid differentiation genes. Additionally, we demonstrate that HIF2 is positively regulated by the pro-differentiation agent all-trans retinoic acid (ATRA), and its inhibition cooperates with ATRA in triggering AML cell differentiation. In conclusion, we report evidence of a new role of HIF2 in the pathogenesis of AML, by promoting an undifferentiated state via EZH2-mediated epigenetic silencing of myeloid differentiation genes. We propose that HIF2 inhibition may open new therapeutic avenues for AML treatment by licensing AML differentiation and synergizing with ATRA towards leukemia exhaustion.
2023-08-10 | GSE175757 | GEO