The transcriptional coactivator Yap promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. Here we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal expansion, as proliferation is counterbalanced by increased apoptosis. To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required. In response to liver injury, Yap drives clonal expansion, suppresses hepatocyte differentiation and promotes a progenitor phenotype. These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair. Overall design: Totally sixteen samples
Two-signal requirement for growth-promoting function of Yap in hepatocytes.
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Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.
Sex, Specimen part, Disease, Cell line, Treatment, Race
View SamplesIdentification of bladder cancer subsets
Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.
Sex
View SamplesExpression profiling of a panel of urothelial cancer cells. The goal of the study is to exam the genome wide expression profile in each of the 30 urothelial cancer cells tested in our laboratory
Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.
Cell line
View SamplesAnalysis of gene expression profiling in FABP4 modulation UM-UC14 and Um-UC9 cells. The overall objective was to identify genes regulated by PPAR signaling pathway in particular FABP4
Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.
Cell line, Treatment
View Samplescharacterize the molecular signature of PB-IMC in different stages of tumor development, thus possibly leading to a novel, sensitive and elegant approach for early cancer detection and surveillance. Overall design: Two types of cancer. For each type 4 groups (day 0, day 4, day 8, day 11), for each group 3 biological repeats
The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.
Specimen part, Cell line, Subject
View SamplesTranslating ribosome affinity purification technology was used to isolate mRNAs from cerebellar Purkinje neurons from control (Pcp2-BacTrap; Rbm17 f/+) and mutant (Pcp2-BacTRAP; Pcp2-Cre; Rbm17 f/-) mice. Overall design: RNA isolation was performed when animals were four-weeks-old (n=3 animals per genotype). Using NuGEN Ovation RNA-Seq System v2, purified double-stranded cDNA was generated from 10 ng of total RNA and amplified using both 3' poly (A) selection and random priming. 2 µg of each sample was sheared using the Covaris S2 focused-ultrasonicator following the manufacturer's protocol to obtain a final library with insert size of 400 bp. The sheared samples were quantified using the NanoDrop ND-1000 spectrophotometer and Invitrogen Qubit 2.0 DNA quantitation assay. The fragment sizes were confirmed on the Agilent Bioanalyzer to verify proper shearing. A double-stranded DNA library was produced using Illumina TruSeq DNA library preparation system and the sequencing was run on a HiSeq 2500 system.
Extensive cryptic splicing upon loss of RBM17 and TDP43 in neurodegeneration models.
Specimen part, Cell line, Subject
View SamplesAged humans and rodents are susceptible to infection with Streptococcus pneumoniae bacteria as a result of an inability to make antibodies to capsular polysaccharides. This is partly a result of decreased production of proinflammatory cytokines and increased production of interleukin (IL)-10 by macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS (169 in only the young, 184 in only the aged, and 500 in both). Expression analysis of systematic explorer revealed that immune response (proinflammatory chemokines, cytokines, and their receptors) and signal transduction genes were specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6 was reduced, and Il10 was increased, confirming our previous results. There was also decreased expression of interferon-gamma. Genes in the Toll-like receptor-signaling pathway leading to nuclear factor-kappaB activation were also down-regulated but IL-1 receptor-associated kinase 3, a negative regulator of this pathway, was increased in aged mice. An increase in expression of the gene for p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding increase in protein expression and enzyme activity confirmed by Western blotting. Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK activity has a role in cytokine dysregulation in the aged mouse Mphi.
Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages.
Specimen part
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YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Specimen part
View SamplesCrypts were isolated from either control or YY1f/f; Vil-Cre-ERT2 mice treated with tamoxifen for 4 days to induce knockout
YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Specimen part
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