Regulation of chromatin accessibility in hypoxia condition
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE200757 | GEO | 2023/03/05
REPOSITORIES: GEO
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Project description:Purpose: Due to its high metastatic proclivity, pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly types of cancer. Therefore, it is imperative to better understand how the disease spreads as it progresses. Using a novel genetically engineered mouse model that allows us to isolate a subpopulation of cancer cells with superior metastatic capacity, we show that this aggressive phenotype correlates exclusively with a strong hypoxia signature. We subsequently identified the novel hypoxia-inducible gene Blimp1, which appears to play a critical role in regulating the hypoxic response upon its induction. Furthermore, genetic ablation of Blimp1 greatly reduces the level of metastasis in a PDAC mouse model. The nature of this Blimp1-regulated hypoxia signature is very unstable, since the seeded metastatic lesions mostly re-adopt similar transcriptomic profiles as the primary tumors. In conclusion, our results offer a potential mechanistic insight into how hypoxia drives metastasis in PDAC. Methods: The liver metastasis cell line 688M was subjected to control or knockdown of Blimp1 before assay. Cells ere validated for knockdown efficiency and then cultured under normoxia and hypoxia (0.5% O2) for 24 hours before preparation for ATAC-Seq (total of 4 groups with 2 technical replicates per group, overall 8 samples). Reference for ATACSeq: Buenrostro et al. 2013. Nat Methods 12:1213-8. Results: For the control knockdown group, 0.5% O2 culture (hypoxia) for 24 hours induced dramatic changes in global genome accessibility, and Blimp1 knockdown appeared to induce minimum changes in chromatin accessibility under hypoxia or normoxia (20% O2). Conclusions: Compared to our RNASeq profiles of the same liver met PDAC cell line under identical conditions, Blimp1 appeared to impact a global gene expression changes under hypoxia that is not associated with a corresponding changes of chromatin accessibility.
2017-08-01 | GSE90918 | GEO
Project description:Regulation of chromatin accessibility in hypoxia condition
| PRJNA826504 | ENA
Project description:Hypoxia is one of the major driving forces mediating tumor angiogenesis, aggressiveness, as well as resistance to chemo- and radiotherapy. It has also been suggested to play important roles in stem cell maintenance for both normal and cancer tissues. However, the mechanisms by which hypoxia-driven epigenetic changes modulate tumorigenesis remain poorly understood. As the histone H3 lysine 9 (H3K9) demethylase Jmjd1a and methyltransferase G9a are upregulated downstream targets of hypoxia, we focused on these two catalytically opposing epigenetic modifiers to address this question. Through the use of homozygous Jmjd1a and G9a knockout mouse embryonic stem (ES) cells, we found that Jmjd1a was not required for stem cell self-renewal and that anti-angiogenesis related genes were epigenetically dysregulated in both Jmjd1a- and G9a deficient ES cells under hypoxic conditions, accompanied by corresponding changes in H3K9 dimethylation and H3K4 trimethylation levels in the proximal promoter regions of these target genes. Most importantly, these genetic alterations led to opposing tumor phenotypes: loss of Jmjd1a results in increased tumor growth, whereas loss of G9a produces smaller tumors. These findings provide new insights on the importance of hypoxia signalling in regulating the epigenetic status and expression of angiogenesis genes that promote tumor progression. 63 microarray samples consisting of 7 mouse ES cell lines of which 2 are wild type (control), 2 Jmjd1a knockout, 2 G9a knockout and 1 G9a knockout that was reconstituted for G9a (G9a control). Each cell line and condition was seeded at 3 different densities (2X10^5, 4X10^5 and 6X10^5) in 6 cm dishes to control for the effects of cell confluency on gene expression. 18 hours after plating, the cells were subjected to normoxia (21% O2) for 24 hours (control), normoxia 20 hours followed by hypoxia (1% O2) for 4 hours (acute hypoxia) and 24 hours hypoxia (chronic treatment). Total RNA was harvested from all samples for microarrays after the 24 hour treatments.
2014-07-30 | E-GEOD-35061 | biostudies-arrayexpress
Project description:Here we derive human and chimpanzee cranial neural crest cells (CNCCs) and profile histone modifications, transcription factors, chromatin accessibility and gene expression to systematically and quantitatively annotate evolutionary divergence of craniofacial cis-regulatory landscapes. Histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K27me3), chromatin modifiers (p300), transcription factors (NR2F1, TFAP2A), chromatin accessibility (ATACseq) and gene expression (RNAseq) were assayed in CNCCs derived from iPSCs/ESCs from 2 chimpanzee and 3 human individuals.
2015-09-11 | E-GEOD-70751 | biostudies-arrayexpress
Project description:We performed single cell ATACseq to measure chromatin accessibility in different subsets of lung dendritic cells hyperglycaemic mice. We used genetic model to achieve hyperglycaemia and compared wild type and Akita mice.
2023-06-29 | E-MTAB-11392 | biostudies-arrayexpress
Project description:To identify genes activated under hypoxia (1%O2) and serum-free treatment of a cancer cell line, we performed cDNA microarray analysis with an ovarian cancer cell line, OVSAYO. Cells were cultured under normoxia /hypoxia (1%O2) and serum-plus/serum-minus conditions for 16 hours. Total RNA was isolated for cDNA microarray analysis.
2015-04-01 | E-GEOD-55564 | biostudies-arrayexpress
Project description:We investigated the effect of low oxygen culture on the proliferation and hair inductive capacity of human dermal papilla cells (DPCs) and dermal sheath cells (DSCs). DPCs and DSCs were cultured in atmospheric/hyperoxia (20% O2), physiological/normoxia (6% O2), or hypoxia (1% O2) conditions, respectively. Proliferation of DPCs and DSCs was highest under normoxia. Hypoxia inhibited proliferation of DPCs but enhanced proliferation of DSCs. In DPCs, hypoxia down-regulated expression of hair inductive capacity-related genes, including BMP4, LEF1, SOX2, and VCAN, and normoxia up-regulated expression of ALP. In DSCs, both normoxia and hypoxia up-regulated SOX2 expression, and hypoxia down-regulated BMP4 expression. Microarray analysis revealed increased expression of pluripotency-related genes, including SPRY, NR0B1, MSX2, IFITM1, and DAZL, under hypoxia. In an in vivo hair follicle reconstitution assay, cultured DPCs and DSCs were transplanted with newborn mouse epidermal keratinocytes into nude mice using a chamber method. In DPCs, normoxia allowed the most efficient induction of hair follicles. In DSCs, hypoxia allowed the most efficient induction and maturation of hair follicles. These results suggest that low oxygen culture enhances the proliferation and maintains functions of human DPCs and DSCs and could be used for skin engineering and clinical applications.
2021-01-21 | GSE125402 | GEO
Project description:We investigated the effect of low oxygen culture on the proliferation and hair inductive capacity of human dermal papilla cells (DPCs) and dermal sheath cells (DSCs). DPCs and DSCs were cultured in atmospheric/hyperoxia (20% O2), physiological/normoxia (6% O2), or hypoxia (1% O2) conditions, respectively. Proliferation of DPCs and DSCs was highest under normoxia. Hypoxia inhibited proliferation of DPCs but enhanced proliferation of DSCs. In DPCs, hypoxia down-regulated expression of hair inductive capacity-related genes, including BMP4, LEF1, SOX2, and VCAN, and normoxia up-regulated expression of ALP. In DSCs, both normoxia and hypoxia up-regulated SOX2 expression, and hypoxia down-regulated BMP4 expression. Microarray analysis revealed increased expression of pluripotency-related genes, including SPRY, NR0B1, MSX2, IFITM1, and DAZL, under hypoxia. In an in vivo hair follicle reconstitution assay, cultured DPCs and DSCs were transplanted with newborn mouse epidermal keratinocytes into nude mice using a chamber method. In DPCs, normoxia allowed the most efficient induction of hair follicles. In DSCs, hypoxia allowed the most efficient induction and maturation of hair follicles. These results suggest that low oxygen culture enhances the proliferation and maintains functions of human DPCs and DSCs and could be used for skin engineering and clinical applications.
2021-01-21 | GSE125401 | GEO
Project description:To investigate the role for LSD1 under hypoxia condition. we depleted LSD1 gene with siRNA in Huh-1 cell lines under 1% O2 hypoxia condtion, and than perforemed gene expression microarray analysis. Using Gene Set Enrichment Analysis (GSEA), determined to identify the biological pathway.
2016-08-10 | GSE85345 | GEO
Project description:The predominant outcome of cardiovascular disease (CVD) is myocardial infarction (MI), where cardiomyocytes are deprived of oxygen. To study inter-individual differences in cardiomyocytes’ response to hypoxia, we established an in vitro model of induced pluripotent stem cell-derived cardiomyocytes from 15 individuals. We characterized gene expression levels, chromatin accessibility, and methylation profiles in these cardiomyocytes in four culturing conditions that correspond to normoxia (10% O2), hypoxia (1% O2) and short or long-term re-oxygenation (back to 10% O2). In our population sample, 2,113 genes change their expression following hypoxia and short- or long-term re-oxygenation. Using available genotypes from all individuals, we identified 1,573 genes with a cis eQTL in at least one of the four culturing conditions. Taking into account the incomplete power to identify eQTLs in any given condition, we also identified 367 dynamic eQTLs, which are classified as eQTLs in at least one, but not in all conditions. A subset of dynamic eQTLs, which are detected only following hypoxia, have not been previously annotated as eQTLs even in much larger collections of heart tissues. We did not detect differences in DNA methylation, or chromatin accessibility as the cells transitioned between normoxia and hypoxia, but we observed a change in chromatin accessibility in 831 genomic regions upon re-oxygenation. Differentially accessible regions are enriched for features of active regulatory regions, SINE elements, and E2F4 transcription factor binding sites . Finally, we found that genes associated with dynamic eQTLs are also associated with complex traits and disease. Our data thus demonstrate how unique genetic effects on gene expression, which are likely relevant for disease, can be uncovered under conditions of stress.
2021-01-28 | GSE144425 | GEO