Liver transplantation is the only therapeutic option for patients with end-stage liver disease. The shortage of donor organs has led to the search for alternative therapies to restore liver function and bridge patients to transplantation. Our previous work has shown that the proliferation of late gestation E19 fetal hepatocytes is mitogen-independent. This is manifested as differences in the control of ribosome biogenesis, global translation, cell cycle progression and gene expression. In the present study, we investigated whether E19 fetal hepatocytes would engraft and repopulate an injured adult liver.
Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
Specimen part
View SamplesWe previously identified the mTOR pathway as critical to progenitor cell proliferation in a model of liver injury, we investigated the temporal activation of mTOR signaling in a rat model of hepatic carcinogenesis. The model employed chemical carcinogens and partial hepatectomy to induce progenitor marker-positive HCC. Rats were administered the mTOR inhibitor rapamycin for a three week period and liver harvested one month following cessation of rapamycin treatment. Short-term rapamycin treatment resulted in a significant reduction of focal lesion burden. Microarray analysis was performed to characterize the gene expression signature of persistent focal lesions in the rapamcyin and placebo treated animals. This analysis revealed a persistent effect of short-term mTORC1 inhibition on gene expression that resulted in a genetic signature reminiscent of normal liver.
Persistent effect of mTOR inhibition on preneoplastic foci progression and gene expression in a rat model of hepatocellular carcinoma.
Sex, Specimen part, Treatment
View SamplesTumors have the capacity to trigger the formation of blood vessels allowing them to spread to other body parts. We examined here the stem cells that form arteries and veins within tumors and propose that their inhibition reduces metastatic spread. Overall design: Examination of dynamics and differentiation of tissue resident endothelial hierarchy in a melanoma setting
Endovascular progenitors infiltrate melanomas and differentiate towards a variety of vascular beds promoting tumor metastasis.
Specimen part, Subject
View SamplesWe assessed how lack of ISG15 influences the levels of transcripts after IFNa stimulation.
Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
No sample metadata fields
View SamplesTwo rat hepatic cell lines, WB-F344 and WB311, were characterized for the effect of rapamycin on gene expression. The WB311 cell line, which is tumorigenic and resistant to the growth inhibitory effects of rapamycin, was originally derived from the WB-F344 parental hepatic epithelial cell line. The goal of this experiment was to identify genes that responded to rapamycin in the sensitive cells but not the resistant cells, thereby providing insight into the mechanism of rapamycin resistance.
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
No sample metadata fields
View SamplesThe interplay between mitogenic and proinflammatory signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. We have used global nuclear run-on coupled with deep sequencing to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated with estradiol, TNFa, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing for estrogen receptor alpha (ERa), the pioneer factor FoxA1 and the p65 subunit of the NF-?B transcription factor. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at the genomic locations encoding for long non-coding RNAs, a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between estrogen and TNFa signaling at the gene level is also evident in the patterns of ERa and NF-?B binding, which relocalize to new binding sites that are not occupied by either treatment alone. Interestingly, the chromatin accessibility of classical ERa binding sites is predetermined prior to estrogen treatment, whereas ERa binding sites gained upon co-treatment with TNFa require NF-?B and FoxA1 to promote chromatin accessibility de novo. Our data suggest that TNFa signaling recruits FoxA1 and NF-?B to latent ERa enhancer locations and directly impact ERa enhancer accessibility. Binding of ERa to latent enhancers upon co-treatment, results in increased enhancer transcription, target gene expression and altered cellular response. This provides a mechanistic framework for understanding the molecular basis for integration of mitogenic and proinflammatory signaling in breast cancer. Overall design: Using GRO-seq and ChIP-seq (ER, FoxA1 and p65) to assay the molecular crosstalk of MCF-7 cells treated with E2, TNFa or both E2+TNFa.
TNFα signaling exposes latent estrogen receptor binding sites to alter the breast cancer cell transcriptome.
No sample metadata fields
View SamplesInfection of RAW264.7 cells with RHku80 parasites or mock-infection for 24 hours
Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates.
Cell line
View SamplesA gene expression profile of BRCAness was defined in publicly available expression data of 61 patients with epithelial ovarian cancer (34 patients with BRCA-1 or BRCA-2 mutations and 27 patients with sporadic disease). This dataset is publicly available at http://jnci.oxfordjournals.org/cgi/content/full/94/13/990/DC1
Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.
Age, Disease stage
View SamplesTranscriptome of murine testis from wild type mice and mice lacking telomerase for three generations (G3-Terc), Ku86 or both telomerase and Ku86.
Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis using mouse models.
No sample metadata fields
View Samples