Endocrine cell ER stress conservation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA997368 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR25388034_1.fastq.gz | Fastqsanger.gz | |||
| SRR25388034_2.fastq.gz | Fastqsanger.gz | |||
| SRR25388035_1.fastq.gz | Fastqsanger.gz | |||
| SRR25388035_2.fastq.gz | Fastqsanger.gz |
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Project description:Endocrine cells are dedicated to the production and processing of hormones, from peptides to small molecules, to regulate key physiological processes including glucose homeostasis and metabolism. Because of this relatively high productivity, endocrine cells must handle a variety of stresses from oxidative stress to the unfolded protein response of the endoplasmic reticulum (UPRER). While much is known about the major pathways regulating the UPRER, the roles of endocrine cell type-specific, context-dependent, and time-dependent transcriptional changes are not well explored. To identify unique and shared responses to the UPRER across a subset of endocrine cell types, we tested representative lines for β-cells (insulin), α-cells (glucagon), δ-cells (somatostatin), X/A-cells (ghrelin), L-cells (glucagon-like peptide 1 (GLP1)), and thyrotropes (thyroid hormone and thyroglobulin). We exposed each cell type to the canonical ER stressor thapsigargin for 6 and 24 h, or vehicle (DMSO 0.1%) for 24 h and performed mRNA sequencing. Analysis of the data showed all lines responded to thapsigargin. Comparisons of up- and down-regulated genes between each line revealed both shared and unique transcriptional signatures. These data represent a valuable mineable set of candidate genes which may have cell type-specific functions during the UPRER, and have the potential to lead to new understanding about how different endocrine cells mitigate or succumb to ER stress.
2025-05-05 | GSE238017 | GEO
Project description:While estrogen receptor positive breast tumors generally respond well to endocrine therapy (ET), up to 40% of patients will experience relapse, either while on endocrine therapy or after ET is completed. We have previously shown that the selective pressure of tamoxifen activates the pro-survival NFkB pathway in patient tumors, breast cancer cell lines, and breast cancer xenograft tumors, and that this activation allows for survival of a population of ET-tolerant cells, which can contribute to relapse after ET withdrawal. Here, we utilized single cell RNA-sequencing to characterize survival pathways in NFkB+, ET-tolerant cells and identified activation of the integrated stress response as a critical survival mechanism. Moreover, we found key players in this pathway are regulated by ET in patient derived organoids. In addition, we developed an ET-tolerant gene signature that can be found in metastatic cell populations and that predicts poor outcome to ET. Our findings suggest that co-targeting of ER and key players in the integrated stress response may be a viable therapeutic strategy to eliminate cells that survive the selective pressure of ET.
2022-03-15 | GSE181812 | GEO
Project description:The majority of breast cancers (BCs) harboring estrogen receptor (ER) have shown endocrine resistance. Our previous study has demonstrated that ferredoxin reductase (FDXR) promotes mitochondrial function and ER+ breast tumorigenesis. Here, integrative analyses of targeted metabolomics assay and gene expression profiling show that FDXR potentiates fatty acid oxidation (FAO) through positive regulation of carnitine palmitoyltransferase 1A (CPT1A) expression. Treatment with ER antagonist (tamoxifen) or degrader (fulvestrant) leads to increased expression of FDXR and CPT1A. In line with this finding, we find that FDXR-CPT1A-FAO axis is required for primary and endocrine resistant breast cancer cell growth. Therapeutically,combining endocrine therapy with FAO inhibitor synergistically reduces primary and endocrine resistant breast cancer cell growth, thus providing a potential combinatory treatment for ER+ breast cancer. We used microarrays to be able to elucidate to some extent the gene regulatory mechanisms of FDXR regulating breast cancer metabolism.
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Project description:Transcriptome profile of Dictyostelium cell during ER-stress
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Project description:Transcriptional profiling of Control and hac1 deletion mutant in ER stress condition on P. angusta DL1 strain. WT+ER stress vs. hac1 deletion mutant+ER stress. Six-condition experiment: Control+ER stress (TM 30, 60, 120min; DTT 30, 60, 120min) vs. hac1 deletion mutant+ER stress condition (TM 30, 60, 120min; DTT 30, 60, 120min) in P. angusta DL1 strain. Independently grown and harvested. Dye-swapping.
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Project description:The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress caused by an impairment of its protein folding capacity. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor that has been conserved during evolution from yeast to mammals; in these organisms, Ire1 transmits information from the ER to the nucleus trough the non-conventional splicing of Hac1 (yeast)/Xbp1 (metazoans) mRNA. We described the Dictyostelium discoideum ER-stress response and characterized its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression program that increases the protein folding capacity of the ER and that alleviates ER protein load. Further, IreA resulted essential not only for cell-survival after TN-induced ER-stress, but also to accomplish about nearly 40% of the transcriptional changes induced upon a TN treatment. In addition, we described that autophagy is activated in Dictyostelium cells after a TN treatment and that autophagy-defective mutants exhibited increased sensitivity to this drug. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway.
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Project description:Here we investigate the impact of epigenetic therapy with Decitabine in endocrine-resistant ER+ breast cancer by using patient-derived xenograft (PDX) models. Decitabine treatment restrained tumour growth, inhibited cell proliferation and resulted in significant loss of DNA methylation, particularly at enhancers and repetitive elements. Systematic integration of matched in situ Hi-C / PCHi-C, EPIC, RNA-seq and ChIP–seq datasets revealed widespread differences in epigenome regulation and enhancer-promoter communication with Decitabine. We find that loss of DNA methylation with Decitabine strongly affects the open (A) and closed (B) compartment structure and TAD boundary insulation. Our study identified and focused on key DNA methylation-dependent, enhancer ER binding sites that are activated in Decitabine-treated PDX tumours, enabling direct interactions between promoters and multiple distal enhancers, inducing expression of ER target genes and pathways. Overall, we demonstrate that epigenetic therapy inhibits tumour progression through to rewiring of ER-mediated 3D chromatin interactions and transcriptome programs. Our findings suggest that targeting the 3D epigenome with epigenetic therapies represents a promising strategy for anti-cancer treatment in ER+ endocrine resistant breast cancer patients.
2021-12-12 | GSE171071 | GEO
Project description:Here we investigate the impact of epigenetic therapy with Decitabine in endocrine-resistant ER+ breast cancer by using patient-derived xenograft (PDX) models. Decitabine treatment restrained tumour growth, inhibited cell proliferation and resulted in significant loss of DNA methylation, particularly at enhancers and repetitive elements. Systematic integration of matched in situ Hi-C / PCHi-C, EPIC, RNA-seq and ChIP–seq datasets revealed widespread differences in epigenome regulation and enhancer-promoter communication with Decitabine. We find that loss of DNA methylation with Decitabine strongly affects the open (A) and closed (B) compartment structure and TAD boundary insulation. Our study identified and focused on key DNA methylation-dependent, enhancer ER binding sites that are activated in Decitabine-treated PDX tumours, enabling direct interactions between promoters and multiple distal enhancers, inducing expression of ER target genes and pathways. Overall, we demonstrate that epigenetic therapy inhibits tumour progression through to rewiring of ER-mediated 3D chromatin interactions and transcriptome programs. Our findings suggest that targeting the 3D epigenome with epigenetic therapies represents a promising strategy for anti-cancer treatment in ER+ endocrine resistant breast cancer patients.
2021-12-12 | GSE171072 | GEO
Project description:Here we investigate the impact of epigenetic therapy with Decitabine in endocrine-resistant ER+ breast cancer by using patient-derived xenograft (PDX) models. Decitabine treatment restrained tumour growth, inhibited cell proliferation and resulted in significant loss of DNA methylation, particularly at enhancers and repetitive elements. Systematic integration of matched in situ Hi-C / PCHi-C, EPIC, RNA-seq and ChIP–seq datasets revealed widespread differences in epigenome regulation and enhancer-promoter communication with Decitabine. We find that loss of DNA methylation with Decitabine strongly affects the open (A) and closed (B) compartment structure and TAD boundary insulation. Our study identified and focused on key DNA methylation-dependent, enhancer ER binding sites that are activated in Decitabine-treated PDX tumours, enabling direct interactions between promoters and multiple distal enhancers, inducing expression of ER target genes and pathways. Overall, we demonstrate that epigenetic therapy inhibits tumour progression through to rewiring of ER-mediated 3D chromatin interactions and transcriptome programs. Our findings suggest that targeting the 3D epigenome with epigenetic therapies represents a promising strategy for anti-cancer treatment in ER+ endocrine resistant breast cancer patients.
2021-12-12 | GSE171070 | GEO
Project description:Here we investigate the impact of epigenetic therapy with Decitabine in endocrine-resistant ER+ breast cancer by using patient-derived xenograft (PDX) models. Decitabine treatment restrained tumour growth, inhibited cell proliferation and resulted in significant loss of DNA methylation, particularly at enhancers and repetitive elements. Systematic integration of matched in situ Hi-C / PCHi-C, EPIC, RNA-seq and ChIP–seq datasets revealed widespread differences in epigenome regulation and enhancer-promoter communication with Decitabine. We find that loss of DNA methylation with Decitabine strongly affects the open (A) and closed (B) compartment structure and TAD boundary insulation. Our study identified and focused on key DNA methylation-dependent, enhancer ER binding sites that are activated in Decitabine-treated PDX tumours, enabling direct interactions between promoters and multiple distal enhancers, inducing expression of ER target genes and pathways. Overall, we demonstrate that epigenetic therapy inhibits tumour progression through to rewiring of ER-mediated 3D chromatin interactions and transcriptome programs. Our findings suggest that targeting the 3D epigenome with epigenetic therapies represents a promising strategy for anti-cancer treatment in ER+ endocrine resistant breast cancer patients.
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