Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA217479 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression was analyzed and compared of normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC cells. The results provide valuable information about the gene expression alterations during the chronic process of liver cancer development. HCC in age-matched male mice were induced by DEN injection. Normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC were freshly isolated and RNA extracted.
2013-10-11 | E-GEOD-50431 | biostudies-arrayexpress
Project description:Gene expression was analyzed and compared of normal mouse hepatocyte, premalignant hepatocytes and fully malignant HCC cells. The results provide valuable information about the gene expression alterations during the chronic process of liver cancer development.
2013-10-11 | GSE50431 | GEO
Project description:Hepatocellular carcinoma (HCC) originates from differentiated hepatocytes undergoing compensatory proliferation in livers damaged by viruses or nonalcoholic steatohepatitis (NASH). While increasing HCC risk, NASH triggers TP53-dependent hepatocyte senescence, which we found to parallel hypernutrition-induced DNA breaks. How this tumor-suppressive response is bypassed to license accumulation of oncogenic mutations and enable HCC progression was previously unknown. We identified the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) as a TP53 target that is elevated in senescent-like NASH hepatocytes but suppressed through promoter hypermethylation and proteasomal degradation in most human HCCs. FBP1 first declines in metabolically-stressed premalignant disease-associated hepatocytes and HCC progenitor cells, paralleling the protumorigenic activation of AKT and NRF2. By accelerating FBP1 and TP53 degradation AKT and NRF2 enhance the proliferation and metabolic activity of previously senescent HCC progenitors. The senescence-reversing NRF2-FBP1-AKT-TP53 metabolic switch, operative in mice and humans, also enhances proliferation-enabled accumulation of DNA damage-induced somatic mutations that drive NASH to HCC progression.
2025-01-10 | GSE266447 | GEO
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
2004-01-02 | GSE887 | GEO
Project description:Objective: Antigen-specific immunotherapy is a promising strategy to treat hepatitis B virus (HBV) infection and (HBV-related) hepatocellular carcinoma (HCC). To facilitate killing of malignant and/or infected hepatocytes, it is vital to know which T cell targets are presented by HLA-I complexes on patient-derived hepatocytes. Here, we aimed to reveal the hepatocyte-specific HLA-I peptidome with emphasis on peptides derived from HBV proteins and tumor associated antigens (TAAs) to guide development of antigen-specific immunotherapy. Design: Primary human hepatocytes were isolated with high purity from (HBV infected) non-tumor and HCC tissues using a newly designed perfusion-free procedure. Subsequently, hepatocyte-derived HLA-bound peptides were identified by mass spectrometry after which source proteins were subjected to gene ontology and pathway analysis. Finally, all HBV-antigen and TAA-derived HLA-peptides were extracted and a selection was tested for immunogenicity. Results: We acquired a high quality HLA-I peptidome of 2x105 peptides, of which source proteins were associated with hepatocyte function. Importantly, we demonstrated HLA-I presentation of HBV-derived and TAA-derived peptides for the first time in immune cell-depleted primary liver cell isolates. The peptidome included 8 HBV-derived peptides and 14 peptides from 8 known HCC-associated TAAs that were exclusively identified in tumor eluates. Of these, immunogenicity was demonstrated for 5 HBV-derived and 3 TAA-derived peptides. Conclusion: We present a first HLA-I immunopeptidome of isolated primary human hepatocytes, devoid of immune cells. Our results directly aid development of antigen-specific immunotherapy for HBV infection and HCC. Described methodology can also be applied to personalize immunotherapeutic treatment of liver diseases in the future.
2022-09-05 | PXD023143 | Pride
Project description:AEG-1 is overexpressed in human hepatocellular carcinoma (HCC) and positively regulates development and progression of HCC A transgenic mouse with hepatocyte-specific expression of human AEG-1 was generated using mouse albumin promoter/enhancer in B6/CBA background. Hepatocytes were isolated from WT and Alb/AEG-1 mice for RNA extraction and Affymetrix microarray hybridization.
2013-07-01 | E-GEOD-46701 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal liver development. We found a major shift in expression of Wnt and RXR-α pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-α gene signature categorized HCCs into two subtypes (high Wnt, low RXR-α and low Wnt, high RXR-α), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-α levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-α achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-α, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target. Total RNA from whole livers taken at different developmental timepoints (embryonic day 14, embryonic day 18, post-natal day 5 and post-natal day 56) along with hepatoblasts isolated from E14 livers and immature hepatocytes isolated from E18 livers was extracted and purified using the Qiagen RNeasy Mini Kit. RNA purity and integrity were assayed by the Bioanalyser 2100 (Agilent Technologies). For each sample, 2 µg of total RNA was reverse transcribed and amplified by using an RNA amplification kit from Ambion. Fifteen micrograms of amplified RNA were labeled by direct chemical coupling to the Cy5 NHS ester (Amersham Biosciences). Normal adult mouse liver (Agilent) was used as control and Cy3 labeled. Labeled RNAs were purified, fragmented, and used as probes to hybridize microarrays. Gene expression profiling was done with the 4x44k mouse Agilent platform. Expression profiling of the 23 human HCC samples was previously described
2015-01-17 | E-GEOD-65063 | biostudies-arrayexpress
Project description:Genomic analysis of human hepatocellular carcinoma (HCC) is potentially confounded by the differentiation state of the hepatic cell-of-origin. Here we integrated genomic analysis of mouse HCC (with defined cell-of-origin) along with normal liver development. We found a major shift in expression of Wnt and RXR-α pathway genes (up and down, respectively) coincident with the transition from hepatoblasts to hepatocytes. A combined Wnt and RXR-α gene signature categorized HCCs into two subtypes (high Wnt, low RXR-α and low Wnt, high RXR-α), which matched cell-of-origin in mouse models and the differentiation state of human HCC. Suppression of RXR-α levels in hepatocytes increased Wnt signaling and enhanced tumorigenicity, whereas ligand activation of RXR-α achieved the opposite. These results corroborate that there are two main HCC subtypes that correspond to the degree of hepatocyte differentation and that RXR-α, in part via Wnt signaling, plays a key functional role in the hepatocyte-like subtype and potentially could serve as a selective therapeutic target.
2015-01-17 | GSE65063 | GEO
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature