Mouse HCC model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE19004 | GEO | 2010/07/01
SECONDARY ACCESSION(S): PRJNA120439
REPOSITORIES: GEO
Similar Datasets
Project description:A mouse model of HCC has been developed based on the reported inactivation of the RB pathway in the majority of human HCC. This mouse model harbors floxed alleles of Rb and p130 genes, as well as germline mutation of the p107 gene. Various strategies to activate the activity of a Cre recombinase leads to the efficient deletion of the three genes in the liver of adult mice (TKO mice). Disruption of the RB pathway induces the rapid development of HCC. These HCCs share many similar features of human HCC. The goal of this array is to assess genome wide expression of TKO HCCs. Gene expression of control livers (n=4) or TKO HCCs (n=5) was measured using the Affymetrix GeneChip Mouse Genome 430-2.0 arrays
2010-07-30 | E-GEOD-19004 | biostudies-arrayexpress
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis.
2014-01-01 | GSE37601 | GEO
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis.
2016-01-01 | GSE37576 | GEO
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb –/–; p107 –/–; p130 –/– (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis. 1 sample of the V/SVZ tissue and the CP tissue
2014-01-01 | E-GEOD-37601 | biostudies-arrayexpress
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb â??/â??; p107 â??/â??; p130 â??/â?? (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis. 4 samples of the V/SVZ (ventricular/subventricular zone) tissue and 4 samples of the CP (cortical plate) tissue
2016-07-03 | E-GEOD-37576 | biostudies-arrayexpress
Project description:Cell cycle deregulation leads to abnormal proliferation and cell death in a context-specific manner. Cell cycle progression driven via Rb pathway forces neurons to undergo S-phase, resulting in cell death associated with the progression of neuronal degeneration. Nevertheless, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons can proliferate and form tumors. Here, we found that differentiating cerebral cortical excitatory neurons underwent S-phase progression but not cell division after acute Rb family inactivation in differentiating neurons. However, the differentiating neurons underwent cell division and form tumors when Rb family members were inactivated in cortical progenitors. Differentiating neurons generated from Rb -/-; p107 -/-; p130 -/- (Rb-TKO) progenitors, but not acutely inactivated Rb-TKO differentiating neurons, activated DNA double-strand break (DSB) repair pathway without increasing the tri-methylation of histone H4 at lysine 20 (H4K20M3), which is known to protect from DNA damage. The activation of DSB repair pathway was essential for the cell division of Rb-TKO differentiating neurons. These results suggest that newly-born cortical neurons from progenitors epigenetically become protected from DNA damage and cell division in a Rb family-dependent manner.
2014-01-01 | GSE37577 | GEO
Project description:Cell cycle deregulation leads to abnormal proliferation and cell death in a context-specific manner. Cell cycle progression driven via Rb pathway forces neurons to undergo S-phase, resulting in cell death associated with the progression of neuronal degeneration. Nevertheless, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons can proliferate and form tumors. Here, we found that differentiating cerebral cortical excitatory neurons underwent S-phase progression but not cell division after acute Rb family inactivation in differentiating neurons. However, the differentiating neurons underwent cell division and form tumors when Rb family members were inactivated in cortical progenitors. Differentiating neurons generated from Rb -/-; p107 -/-; p130 -/- (Rb-TKO) progenitors, but not acutely inactivated Rb-TKO differentiating neurons, activated DNA double-strand break (DSB) repair pathway without increasing the tri-methylation of histone H4 at lysine 20 (H4K20M3), which is known to protect from DNA damage. The activation of DSB repair pathway was essential for the cell division of Rb-TKO differentiating neurons. These results suggest that newly-born cortical neurons from progenitors epigenetically become protected from DNA damage and cell division in a Rb family-dependent manner. 3 samples of pCAG-control, pCAG-RbTKO, pMAP2-control, and pMAP2-RbTKO cells
2014-01-01 | E-GEOD-37577 | biostudies-arrayexpress
Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program. Experiment Overall Design: Expression profiles of IMR90 cells before and after RNAi-mediated supppression of RB, p107 or p130 in growing, quiescent or ras-induced senescent conditions. RNA was extracted from growing, low serum (0.1% FBS), confluent, or ras-senescent cells.
2010-01-23 | E-GEOD-19864 | biostudies-arrayexpress
Project description:The action of RB as a tumor suppressor has been difficult to define, in part, due to the redundancy of the related proteins p107 and p130. By coupling advanced RNAi technology to suppress RB, p107 or p130 with a genome wide analysis of gene expression in growing, quiescent or ras-senescent cells, we identified a unique and specific activity of RB in repressing DNA replication as cells exit the cell cycle into senescence, a tumor suppressive program.
2010-01-15 | GSE19864 | GEO
Project description:The epidermal-specific ablation of Rb gene leads to increased proliferation, aberrant differentiation, and the disengagement of these processes in vivo and in vitro. These differences in phenotype are more severe with the loss of p107, demonstrating the functional compensation between pRb and p107. As p107 and p130 also exert overlapping functions in epidermis, we have generated Rb(F19/F19)K14cre;Rbl2-/- (pRb-;p130-) mice to analyze possible functional redundancies between pRb and p130. The epidermal phenotype was very similar between pRb- and pRb-;p130- mice, suggesting that pRb and p130 activities are not redundant in epidermis. Importantly, we can correlate the proliferation differences with specific changes in gene expression between pRb-, pRb-;p107- and pRb-;p130- primary keratinocytes using microarray analysis, and explain the phenotypes in the context of altered E2F expression and functionality. Our findings support a model in which the distinct retinoblastoma family members, in conjunction with E2F members, play a central role in regulating epidermal homeostasis through specific or overlapping activities. Keywords: skin, pRb, transgenic mice, p130
2007-11-13 | GSE9562 | GEO