Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell RNA sequence data from intrahepatic immune cells of CHB(chronic hepatitis B) mice

ABSTRACT: We successfully established a novel immunocompetent mouse model of CHB(chronic hepatitis B) at the immune-active phase by a simple combination of a Fumarylacetoacetate hydrolase (FAH) knockout mouse, hydrodynamic tail vein injection, and sleeping-beauty transposon system. The employment of single-cell RNA sequence in this model revealed the comprehensive intrahepatic immune landscape in the immune-active phase, which contributes to the persistence of HBV infection. Our model also made it possible to profile the intrahepatic immune response to the immunomodulators.

ORGANISM(S): Mus musculus

PROVIDER: GSE271816 | GEO | 2024/12/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of mouse wild type, Fah and Fah, p21 ON and OFF NTBC animals

Project description:Fumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency. Experiment Overall Design: Livers from adult wildtype, Fah or Fah, p21 knockout mice were analyzed either after continuous treatment (ON) with NTBC or after NTBC withdrawal for 14 days (OFF).

2008-06-11 | E-GEOD-11098 | biostudies-arrayexpress

Global gene expression profiles of mouse ESCs, disease-specific iPSCs, and gene-corrected iPSCs

Project description:The use of patient-derived induced pluripotent stem (iPS) cells as treatment for genetic diseases entails genetic repair or transfer of genetic information as a prerequisite. We have chosen the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase deficiency; FAH(-/-) mice) as a paradigm for hereditary metabolic liver disorders and evaluated fibroblast-derived FAH(-/-)-iPS cell lines as targets for gene correction. By aggregating FAH(-/-)-iPS cells with tetraploid embryos, we obtained FAH-/--iPS cellâderived mice, which exhibited the phenotype of the founding FAH(-/-)-mice. We then rescued the diseased phenotype by lentiviral transduction of FAH-cDNA and performed embryo aggregation with these gene-corrected FAHgc-iPS cells to obtain viable healthy mice. Our results demonstrate that iPS cell technology is a valid approach to establish mouse disease models directly from somatic cells bearing genetic defects. Furthermore, established iPS cell lines can be genetically manipulated without loss of pluripotency for treatment of genetic diseases. 6 samples: 1 MEF, 1ESC, 4 iPSCs

2010-04-28 | E-GEOD-21343 | biostudies-arrayexpress

Human hepatocyte metaplasia in injured humanized mouse livers

Project description:The goal of this experiment was to test whether human hepatocytes could give rise to biliary-like progenitor cells in an in vivo context. Here Fah-/- Il2ry-/- Rag2-/-NOD mouse livers were humanized with human hepatocytes. Only hepatocytes engraft in the Fah-/- mouse at detectable levels in this model. Then animals were given chronic liver injury with 0.1% ddc. After injury we measured human-specific transcripts to determine whether the phenotype of the human cells had changed. Specifically, we evaluated the relative levels of human biliary duct markers such as Spp1, Sox9, Krt7, etc. and hepatocyte markers such as Alb, Ttr, Fah, etc. 3 DDC treated chimeras and 6 untreated chimeras are included. Additional controls include a normal human liver biopsy, FACS sorted primary intrahepatic human bile duct cells, mouse hepatocytes, and mouse intrahepatic biliary cells in ddc treated animal.

2014-09-01 | E-GEOD-58679 | biostudies-arrayexpress

Wildtype, Fah and Fah, p21 ON and OFF NTBC

2008-04-09 | GSE11098 | GEO

Genomic and epigenomic characterization of regenerating hepatocytes

Project description:To gain a deeper understanding of the genetic basis of liver repopulation after injury, we utilize an innovative technique to profile the expression changes and chromatin landscape during the regenerative response. We utilize the Fah-/- mouse, a model for hereditary tyrosinemia deficient in fumarylacetoacetate hydrolase (FAH), that undergoes repopulation with FAH-expressing hepatocytes. We employ translating ribosome affinity purification followed by RNA-sequencing (TRAP-seq) and assay for transposase accessible chromatin using sequencing (ATAC-seq) to specifically isolate regenerating hepatocytes and performed high-throughput sequencing to identify the dynamic genomic and epigenomic changes during liver repopulation.

2018-01-24 | GSE109466 | GEO

Global gene expression profiles of mouse ESCs, disease-specific iPSCs, and gene-corrected iPSCs

Project description:The use of patient-derived induced pluripotent stem (iPS) cells as treatment for genetic diseases entails genetic repair or transfer of genetic information as a prerequisite. We have chosen the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase deficiency; FAH(-/-) mice) as a paradigm for hereditary metabolic liver disorders and evaluated fibroblast-derived FAH(-/-)-iPS cell lines as targets for gene correction. By aggregating FAH(-/-)-iPS cells with tetraploid embryos, we obtained FAH-/--iPS cell–derived mice, which exhibited the phenotype of the founding FAH(-/-)-mice. We then rescued the diseased phenotype by lentiviral transduction of FAH-cDNA and performed embryo aggregation with these gene-corrected FAHgc-iPS cells to obtain viable healthy mice. Our results demonstrate that iPS cell technology is a valid approach to establish mouse disease models directly from somatic cells bearing genetic defects. Furthermore, established iPS cell lines can be genetically manipulated without loss of pluripotency for treatment of genetic diseases.

2010-04-16 | GSE21343 | GEO

Aneuploidy as a mechanism for stress-induced liver adaptation

Project description:Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question whether this unusual somatic genetic variation evolved as an adaptive mechanism to hepatic injury. According to this model, hepatotoxic insults would select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to the injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in homogentisic acid dioxygenase (Hgd), located on chromosome 16. Loss of this allele can protect from fumarylacetoacetate hydrolase (Fah) deficiency. When adult Hgd+/- Fah-/- mice were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16-specific aneuploidy was ~50%. This result provides proof-of-principle that the selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans is under investigation. 8 mouse hepatocyte samples were analyzed. Genomic DNA samples were derived from wild type mice (2), Hgd-/- Fah-/- mice off NTBC (2) and Hgd+/- Fah-/- off NTBC (4). Samples were compared to sex-mismatched reference genomic DNA isolated from wild type mouse splenocytes.

2012-07-16 | E-GEOD-38963 | biostudies-arrayexpress

Genome-wide transcriptional analysis of metabolism-related genes and pathways regulated by FAH in melanoma A375 cells

Project description:Reprogramming metabolism plays an important role in tumor cells for maintaining their abnormal biologic behaviors. Therefore, special factors could regulate metabolic processes and influence the overall status of tumor cells. This phenomenon was obviously found in melanoma. Fumarylacetoacetate hydrolase (fumarylacetoacetase, FAH) is an enzyme encoded by the FAH gene located on the chromosome 15q25.1 region and contains 14 exons. FAH enzyme catalyzes the hydrolysis of 4- fumarylacetoacetase into fumarate and acetoacetate. It is the last enzyme in the subpathway from L-phenylalanine and tyrosine degradation. Mutations in the FAH gene cause type I tyrosinemia, which is a hereditary error of metabolism that is characterized by increased tyrosine levels in the blood and urine of patients. In the present study, we will explore whether FAH is an essential enzyme to promote multiple metabolic processes and elucidate the functions of FAH in melanoma. Gene microarrays and bioinformatics analysis of the differentially expressed genes (DEGs) were performed using A375 cells, and we concentrated on the biologic functions of FAH. In general, our work revealed several functional mechanisms of FAH in melanoma, which indicated FAH might be a potentially therapeutic target and an independent prognostic indicator for this disease.

2018-02-14 | GSE86870 | GEO

Gene expression profiling of Fah-deficient mouse livers upon short-term nitisinone discontinuation

Project description:Hereditary tyrosinemia type 1 (HT1) is a severe genetic disorder that affects the liver due to a defective fumarylacetoacetate hydrolase (Fah) enzyme in hepatocytes. The drug nitisinone (NTBC) has offered a life-saving treatment for HT1 patients by inhibiting the upstream enzyme 4-hydroxyphenylpyruvate dioxygenase (HPD). We used microarray analyses to define the impact of short-term (ie. seven days) NTBC therapy discontinuation on the gene expression profile of liver tissue of Fah-deficient mice. Consequently, we investigated the modulation of canonical pathways related to oxidative stress, glutathione metabolism and liver regeneration.

2020-12-23 | GSE161478 | GEO

Gene expression profiling of Fah-deficient mouse livers upon short-term nitisinone discontinuation

2023-06-03 | GSE205434 | GEO