Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mycobacterial tuberculosis infection in hypoxia-inducible factor-1alpha deficient macrophages

ABSTRACT: We herein found the strong expression of hypoxia-inducible factor-1α (HIF-1α) in tuberculosis granulomas and more rapid death of HIF-1α-conditional knockout mice than wild-type mice after M. tuberculosis infection. These results prompted us to investigate the role of HIF-1α in host defenses against infection. Bone-marrow derived macrophages from Wild-type (WT) mice and HIF-1α-conditional knockout (HIF-1 CKO) mice were infected with M tuberculosis H37Rv (multiplicity of infection = 0.5) for 12 h, and extracellular bacilli were removed from the macrophage culture medium. Cells were cultured for 4 days in the presence of 500 U/ml IFN-γ. In microarray analysis using Gene Chip Mouse Gene 1.0 ST Array, the expression of 757 and 1190 genes was ≥1.3-fold stronger and ≥0.77-fold weaker, respectively, in HIF-1 CKO than in WT.

ORGANISM(S): Mus musculus

SUBMITTER: Mayuko Osada-Oka

PROVIDER: E-MTAB-7244 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis

Project description:Bone is a highly dynamic tissue undergoing continuous formation and resorption. Here, we investigated differential but complementary roles of hypoxia-inducible factor (HIF)-1α and HIF-2α in regulating bone remodeling. Using RNA-seq analysis, we identified that specific genes involved in regulating osteoblast differentiation were similarly but slightly differently governed by HIF-1α and HIF-2α. We found that increased HIF-1α expression inhibited osteoblast differentiation via inhibiting RUNX2 function by upregulation of Twist2, confirmed using Hif1a conditional knockout (KO) mouse. Ectopic expression of HIF-1α via adenovirus transduction resulted in the increased expression and activity of RANKL, while knockdown of Hif1a expression via siRNA or osteoblast-specific depletion of Hif1a in conditional KO mice had no discernible effect on osteoblast-mediated osteoclast activation. The unexpected outcome was elucidated by the upregulation of HIF-2α upon Hif1a overexpression, providing evidence that Hif2a is a transcriptional target of HIF-1α in regulating RANKL expression, verified through an experiment of HIF-2α knockdown after HIF-1α overexpression. The above results were validated in an ovariectomized- and aging-induced osteoporosis model using Hif1a conditional KO mice. Our findings conclude that HIF-1α plays an important role in regulating bone homeostasis by controlling osteoblast differentiation, and in influencing osteoclast formation through the regulation of RANKL secretion via HIF-2α modulation.

2024-07-10 | GSE271730 | GEO

RNA-seq on enriched cardiac fibroblasts from the hearts of Hif-1a conditional knockout or heterozygous mice

Project description:In this project we explore the role of the master hypoxia regulator, Hypoxia inducible factor-1alpha (Hif-1a), in governing cardiac fibroblast (CF) function in homeostasis. CF-specific Hif-1a conditional knockout (cKO) mice were generated by breeding Pdgfra-merCremer (PdgfraMCM/+) Cre recombinase driver mice with Hif-1a-floxed mice (Hif-1aflox/). In Hif-1afl/-; PdgfraMCM/+ progeny, Hif-1a could be conditionally deleted in adult CFs by tamoxifen (tam) administration. We also introduced a Cre-dependent R26tdTomato reporter allele allowing marking of Pdgfra+ CFs and their progeny. In this experiment, we performed bulk RNA sequencing (RNA-seq) on tdTomato+ cells from the hearts of healthy cKO or heterozygous (HET) adult, male mice.

2021-11-11 | E-MTAB-9674 | biostudies-arrayexpress

Dissecting the Mycobacterium bovis BCG response to macrophage infection to identify targets for anti-tuberculosis drug and vaccine discovery

Project description:New strategies are required to reduce the worldwide burden of tuberculosis. Intracellular survival and replication of Mycobacterium tuberculosis after macrophage phagocytosis is a fundamental step in the complex host-pathogen interactions that lead to granuloma formation and disease. Greater understanding of how the bacterium survives and thrives in these environments will inform novel drug and vaccine discovery programmes. Here, we use in-depth RNA sequencing of Mycobacterium bovis BCG from human THP-1 macrophages to describe the mycobacterial adaptations to the intracellular environment. We identify 329 significantly differentially regulated genes, highlighting cholesterol catabolism, methyl-citrate cycle and iron homeostasis as important for mycobacteria inside macrophages. Focused analysis of PE/PPE and cytochrome P450 gene families highlight additional pathways that are upregulated (35 and five respectively) 24h after infection. Comparison of the intracellular transcriptome to gene essentiality and immunogenicity studies identified 15 potential targets that are both required for intracellular survival and induced on infection, and eight genes upregulated that have been demonstrated to be immunogenic in TB patients. Further insight into these new and established targets will support drug and vaccine development efforts.

2022-01-14 | E-MTAB-11107 | biostudies-arrayexpress

Single-cell RNA-seq on enriched cardiac fibroblasts from the healthy, sham or MI hearts of Hif-1a conditional knockout or heterozygous mice

Project description:In this project we explore the role of the master hypoxia regulator, Hypoxia inducible factor-1alpha (Hif-1a), in governing cardiac fibroblast (CF) function in homeostasis and following an acute ischaemic injury - myocardial infarction (MI). CF-specific Hif-1a conditional knockout (cKO) mice were generated by breeding Pdgfra-merCremer (PdgfraMCM/+) Cre recombinase driver mice with Hif-1a-floxed mice (Hif-1aflox/). In Hif-1afl/-; PdgfraMCM/+ progeny, Hif-1a could be conditionally deleted in adult CFs by tamoxifen (tam) administration. We also introduced a Cre-dependent R26tdTomato reporter allele allowing marking of Pdgfra+ CFs and their progeny. In this experiment, we first performed single-cell RNA sequencing (scRNA-seq) on tdTomato+ cells from the hearts of healthy cKO or heterozygous (HET) adult, male mice using the 10x Genomics Chromium system. We also performed scRNA-seq on tdTomato+/CD31-/CD45- cells from the hearts of cKO or HET mice at day-3 post-sham or -MI surgery.

2021-11-11 | E-MTAB-9583 | biostudies-arrayexpress

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis-HIF-1α axis (scRNA-Seq)

Project description:Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs) that are critical for orchestrating the anti-inflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxic response through hypoxia-inducible factor-1 alpha (HIF-1α) were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted HIF-1α conditional knockout mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. In addition, scRNA-seq analysis of granulocytes from PJI patients also showed an enrichment in glycolysis and hypoxic response genes. These findings support the importance of a glycolysis/HIF-1α axis in promoting G-MDSC anti-inflammatory activity and biofilm persistence during PJI.

2024-01-23 | GSE241950 | GEO

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis-HIF-1α axis

2024-02-08 | GSE248055 | GEO

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis-HIF-1α axis II

2024-02-08 | GSE241739 | GEO

Granulocytic myeloid-derived suppressor cell activity during biofilm infection is regulated by a glycolysis-HIF-1α axis I

2024-02-08 | GSE241698 | GEO

HIF-1α activation is sufficient for the development of MDS

Project description:Hypoxia inducible factor-1α (HIF-1α) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1α is also a key regulator for immune cell activation. In order to determine whether HIF-1α is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1α transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1α can be induced in a doxycycline administration dependent manner. After induction, HIF-1α-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1α- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1α is sufficient to trigger a variety of key MDS features

2018-12-25 | GSE83988 | GEO

Activating injury-responsive genes with hypoxia enhances axon regeneration through neuronal HIF-1α

Project description:Injured peripheral neurons successfully activate a pro-regenerative transcriptional program to enable axon regeneration and functional recovery. How transcriptional regulators coordinate the expression of such programs remains unclear. Here we show that hypoxia-inducible factor 1α (HIF-1α) controls multiple injury-induced genes in sensory neurons and contribute to the pre-conditioning lesion effect. Knockdown of HIF-1α in vitro or conditional knockout in vivo impairs sensory axon regeneration. The HIF-1α target gene Vascular Endothelial Growth Factor A (VEGFA) is expressed in injured neurons and contributes to stimulate axon regeneration. Induction of HIF-1α using hypoxia enhances axon regeneration in vitro and in vivo in sensory neurons. Hypoxia also stimulates motor neuron regeneration and accelerates neuromuscular junction reinnervation. This study demonstrates that HIF-1α represents a critical transcriptional regulator in regenerating neurons and suggests hypoxia as a tool to stimulate axon regeneration.

2016-01-21 | GSE73415 | GEO

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