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Transcriptome profile of ATP7B KO cells and WT cells treated with Copper (Cu) to study Autophagy as a pro-survival mechanism in Wilson disease

ABSTRACT: Transcriptome profile of ATP7B KO cells and WT cells treated with Copper (Cu) to study Autophagy as a pro-survival mechanism in Wilson disease

PROVIDER: PRJNA419762 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6321980.fastq.gz	Fastqsanger.gz
	SRR6321981.fastq.gz	Fastqsanger.gz
	SRR6321982.fastq.gz	Fastqsanger.gz
	SRR6321973.fastq.gz	Fastqsanger.gz
	SRR6321983.fastq.gz	Fastqsanger.gz

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Transcriptome profile of ATP7B KO cells and WT cells treated with Copper (Cu) to study Autophagy as a pro-survival mechanism in Wilson disease

Project description:To understand whether hepatic cells use autophagy to defend against Cu toxicity in WD, we employed ATP7B knockout (ATP7B-KO) HepG2 cell line, by Quant-seq experiments. Transcriptome analysis of the of ATP7B KO cells and WT cells treated with Copper (Cu) compared with untreated cells.

2019-02-26 | GSE107323 | GEO

Screening for genes that promote copper toxicity in a cell model of Wilson disease [HepG2 cells ATP7B-KO]

Project description:To find new genes that might be targeted for reduction of Copper (Cu) toxicity in Wilson disease we employed genome-wide shRNA screening in ATP7B-KO HepG2 cells, a bona fide WD cell model. Cells were screened using the Dharmacon™ Decode™ Pooled Lentiviral shRNA Screening Library targeting 18205 human genes (Dharmacon #RHS6083). The Lentiviral RNAi screening library is made of 10 pools of 9570 GIPZ short hairpin RNAs (shRNAs) packaged into high-titer lentiviral particles. Genomic DNA was isolated from the cells and read counts for each shRNAs were obtained by deep sequencing to determine the abundance of each shRNA in the Cu-treated cells compared to controls. This analysis allowed the identification of genes whose downregulation promoted survival of ATP7B-KO cells upon Cu overload. To exclude that some shRNAs would have been responsible for ATP7B-KO survival by suppressing generic proapoptotic genes, we run the same screening with the proapoptotic drug vinblastine instead of CuCl2. Genes, whose suppression allowed cell to resist Cu but not vinblastine were considered as Cu-specific hits and through this approach we identified PrP as a suitable target for reduction of Cu toxicity in WD. Indeed, we found that Cu accumulation in ATP7B-KO cells stimulates expression of PrP, which brings to toxic Cu overload while PrP suppression significantly reduces Cu accumulation and toxicity in ATP7B-deficient cells. In sum our data highlight an important regulatory role of PrP in copper metabolism and as a therapeutic tool for Wilson disease.

2024-12-09 | GSE277865 | GEO

Screening for genes that promote copper toxicity in a cell model of Wilson disease

2024-12-09 | GSE260454 | GEO

Specific changes of liver transcriptome in the early stages of copper accumulation in the mouse model of wilson disease

Project description:Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways. Keywords: comparative genomic hybridization

2006-12-19 | GSE5348 | GEO

Transcription profiling of mouse model of Wilson disease reveals specific changes of liver transcriptome in the early stages of copper accumulation

2008-06-13 | E-GEOD-5348 | biostudies-arrayexpress

Interactomes of WT and H1069Q variants of ATP7B

Project description:The H1069Q substitution in the liver-specific copper transporter ATP7B represents the major cause of Wilson disease. The mutated ATP7B undergoes rapid degradation in the endoplasmic reticulum (ER) and fails to reach copper excretion compartments thus causing severe copper toxicosis in patients. Modulating the ATP7B-H1069Q interactome was proposed as a rescue strategy but specific binding partners that might be targeted for mutant correction remain elusive. Here we try to identify a mutant-specific interactor for the pharmacological rescue of ATP7B-H1069Q.

2020-12-11 | PXD016816 | Pride

TRANSCRIPTIONAL REMODELLING IN RESPONSE TO CHANGING COPPER LEVELS IN WILSON DISEASE MODEL OF SACCHAROMYCES CEREVISIAE

Project description:A 3 x 2 factorial design was used to elucidate the genome-wide transcriptional response to the deletion of yeast ortholog of Wilson and Menkes disease causing gene; CCC2, at changing copper levels. Homozygous deletion mutant of CCC2, which encodes Cu+2 transporting P-type ATPase required to export copper from the cytosol into the extracytosolic compartment, and the reference strain were cultivated in fully controlled fermenters in duplicates in glucose-rich defined medium containing three different levels of copper. The three different copper concentrations were selected such that; copper deficient condition, which was prepared by excluding the CuSO4.7H2O from the defined medium, low copper or adequate copper concentration, which is the standard amount of copper in defined medium (0.04 ?M) and high copper concentration (0.5 mM), which was able to restore respiration deficiency in ccc2?/ccc2? strain.

2013-09-02 | E-MEXP-3927 | biostudies-arrayexpress

ATP7B Gene Therapy of Autologous Reprogrammed Hepatocytes Alleviates Copper Accumulation in a Murine Model of Wilson’s Disease

Project description:Purpose：Wilson's disease (WD) is a rare hereditary disorder due to ATP7B gene mutation, causing pathologic copper storage mainly in the liver and neurological systems. Hepatocyte transplantation showed therapeutic potential, however, this strategy is often hindered by a shortage of quality donor cells and by allogeneic immune rejection. Here we evaluate the function and efficacy of autologous reprogrammed, ATP7B gene-restored hepatocytes using a murine model of WD Mathods and Results: By reprogramming hepatocytes from ATP7B-/- mice with small molecules, sufficient liver progenitor cells (LPCs) are harvested. After lentivirus-mediated miniATP7B gene transfection and re-differentiation, functional LPC-ATP7B-Heps are developed. RNA-seq data show that compared with LPC-GFP-Heps with enrichment of genes mainly in pathways of oxidative stress and cell apoptosis, in LPC-ATP7B-Heps under high copper stress pathways for copper ion binding and cell proliferation are enriched. LPC-ATP7B-Heps transplantation into ATP7B-/- mice alleviates deposition of excess liver copper with its associated inflammation and fibrosis, comparable to those observed using normal primary hepatocytes at four months after transplantation. Conclusion: We establish the autologous reprogrammed, ATP7B gene restored LPC-ATP7B-Heps and further transplantation demonstrate alleviated copper accumulation in WD mice.

2022-03-05 | GSE197948 | GEO

RNA Sequencing in LXR agonist fed Atp7b-/- mice (Wilson disease)

Project description:RNA Sequencing in LXR agonist fed Atp7b-/- mice (Wilson disease)

| PRJNA728814 | ENA

Screening for genes that promote copper toxicity in a cell model of Wilson disease [HepG2 cells ATP7B-KO]

Project description:Screening for genes that promote copper toxicity in a cell model of Wilson disease [HepG2 cells ATP7B-KO]

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