Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hypoxia inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair

ABSTRACT: Following myocardial infarction, tissue ischemia leads to activation of hypoxia inducible factors. DeBerge et al. demonstrate that HIF-1a and HIF-2a activation in myeloid cells antagonizes cardiac repair pathways through cleavage of cardioprotective MerTK and suppression of anti-inflammatory mitochondrial metabolism, respectively.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180678 | GEO | 2021/07/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

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

2012-02-25 | GSE27523 | GEO

Heterogeneous effects of massive hypoxia pathway activation in kidney cancer

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

2015-07-10 | E-GEOD-67237 | biostudies-arrayexpress

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

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

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

2014-03-25 | GSE56141 | GEO

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

ChIP-seq analysis of HIF-1a and HIF-2a binding in hypoxic cancer cell lines

Project description:Pan-genomic analysis of hypoxic HIF-1a and HIF-2a binding by ChIP-seq in cancer cell lines

2022-11-15 | GSE200203 | GEO

Heterogeneous effects of massive hypoxia pathway activation in kidney cancer

2015-07-10 | GSE67237 | 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

Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair.

Project description:Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

| S-EPMC8329871 | biostudies-literature

HIF knockdowns in human hematopoietic stem cells

Project description:Hematopoietic stem cells (HSCs), which reside in bone marrow niches, are exposed to low levels of oxygen and follow an oxygen gradient throughout their differentiation. Hypoxia-inducible factors (HIFs) are the main factors regulating the cell response to oxygen variation. Recent studies using conditional knockout mouse models have unveiled a major role of HIF-1a in the maintenance of murine HSCs, however the role of HIF-2a is still unclear. Here, we show that knockdown of HIF-2a and to a much lower extent, HIF-1a impedes the long-term repopulating ability of human CD34+ umbilical cord blood derived cells. The defects observed in hematopoietic stem and progenitor cell (HSPC) function after HIF-2a knockdown was due to an increase in the production of reactive oxygen species (ROS), which increases the endoplasmic reticulum (ER) stress in HSPCs and triggers apoptosis by the activation of the unfolded-protein-response (UPR) pathway. Importantly, HIF-2a deregulation also resulted in a significant decrease of engraftment of human acute myeloid leukemia (AML) cells. Overall, our data demonstrates a key role of HIF-2a in the maintenance of human HSPCs and in the survival of primary AML cells. 2 controls and 2 shHIF2 CD34+ cell samples sorted from mice after 6 weeks of engraftment

2014-01-01 | E-GEOD-49897 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data