The objective is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired and, thus, will provide a continuous stimulus to the cell. Cells lacking Artemis and Atm are used to determine which gene expression changes depend on Atm and cells lacking Artemis that express an I kappa B alpha dominant negative are used to determine which gene expression changes depend on NFkB.
DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes.
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View SamplesE14 TG2a cells grown with LIF were disaggregated and FACS sorted for cell surface 5T4 negativity versus E14 TG2a cells grown without LIF for 3 days and sorted for 5T4 positivity.
CXCR4 mediated chemotaxis is regulated by 5T4 oncofetal glycoprotein in mouse embryonic cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Sex, Specimen part, Disease, Treatment
View SamplesGene-expression profiles of rat liver cirrhosis induced by diethylnitrosamine and the effect of erlotinib on liver fibrogenesis and liver cancer development
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Sex, Specimen part, Disease, Treatment
View SamplesGene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated mouse and the effect of erlotinib
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Specimen part, Treatment
View SamplesGene-expression profiles of rat hepatocellular carcinoma induced by diethylnitrosamine (DEN) and the effect of erlotinib
Epidermal growth factor receptor inhibition attenuates liver fibrosis and development of hepatocellular carcinoma.
Specimen part, Treatment
View SamplesPurpose: Tracheal epithelial brush cells are rare chemosensory cells defined by their expression of elements of the bitter taste transduction system, and known to activate the cholinergic nervous system in the murine lung. Similar chemosensory cells in the intestine can generate lipid mediators and pro-inflammatory cytokines but whether brush cell can contribute to airway inflammation is unknown. Furthermore, despite the advances in understanding chemosensory cell effector functions, the receptors that mediate chemosensory cell activation and expansion beyond taste receptors in any compartment remain largely unknown. Methods: In this study, we isolated tracheal brush cells by FACS from naïve ChATBAC-eGFP mice with knockin of eGFP within a BAC spanning the acetylcholine transferase locus, marking brush cells in the epithelium and performed transcriptome profiling using low input RNA sequencing. We compared tracheal brush cells to EpCAM+ epithelial cells and CD45+ hematopoetic cells in naive mice. Results: When compared to EpCAM+ EpCs and to CD45+ cells in the airway, principal component analysis demonstrated that brush cells grouped quite distinctly. This brush cell distinction relative to EpCAM+ cells, was further reflected in the striking number of highly differentially expressed genes. This included 1305 genes expressed at 4-fold or higher levels in EpCAM+eGFP+ cells (brush cells), of which 418 genes were expressed at 32-fold or higher levels in brush cells. Conclusions: Our study represents the first detailed analysis of the transcriptome of tracheal brush cells and identifies a unique set of genes that are primarily expressed in brush cells including the bitter taste transduction system, synthenic machinery for several pro-inflammatory lipid mediators and HoxA2 transciptional factors. Overall design: Examination of gene expression of tracheal brush cells (ChAT-eGFP), EpCAM+ (EpCAM) tracheal epithelial cell and CD45+ hematopoetic cells in naïve mice.
The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing airway brush cells leading to type 2 inflammation.
Specimen part, Cell line, Subject
View SamplesCD33-/- and/or TREM2-/- mice were crossed with the 5xFAD mouse model of Alzheimer's disease to generate single and double CD33/TREM2 knock-out mice on 5xFAD background. Transcriptome and gene expression analyses were performed to analyze the impact of CD33 and/or TREM2 knock-out on the transcriptome of microglia in the context of amyloid pathology. The results revealed that CD33 and/or TREM2 knock-out reprogrammed microglial gene expression signatures in 5xFAD mice in an age-dependent manner. Differential gene expression in 5xFAD;CD33-/- microglia depended on the presence of TREM2. These data suggest that TREM2 acts downstream of CD33. Overall design: Microglia were isolated from brains of WT, 5xFAD, 5xFAD;CD33-/-, 5xFAD;TREM2-/-, and 5xFAD;CD33-/-;TREM2-/- mice at 4 and 8 months of age, using FACS sorting for CD11b and CD45. RNA was extracted using the RNeasy Plus Micro Kit (Qiagen). Libraries were prepared using the TruSeq Stranded mRNA LT Prep Kit (Illumina) and sequenced on an Illumina HiSeq 2500 sequencer using single-end 50. Reads were aligned to mouse genome mm10 using the STAR aligner. Read counts for individual genes were obtained using HTSeq.
TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer's Disease.
Age, Cell line, Subject
View SamplesWe surveyed the transcriptomes of the whole heart and whole gastrocnemius muscle taken from two different types of Balb/c-DBAj hybrid mice (10-11 weeks old). The colon cancer bearing mice are called C26. The NTB are the non-tumor bearing mice.
Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia.
Specimen part
View SamplesThe MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, raising the possibility that MYB may be a therapeutic target. However realization of this potential requires (i) a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis; and (ii) an approach for developing an effective therapeutic. We previously showed that the interaction of Myb with the coactivator CBP/p300 is essential for its transforming activity. Here we use hematopoietic cells from the Booreana mouse strain, which carries a mutation in Myb that prevents interaction with CBP/p300, to examine the requirement for this interaction in myeloid transformation and leukemogenesis. Using this strain and a strain (plt6) carrying a complementary mutation in p300, we show that the Myb-p300 interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type (WT) mice, Booreana cells fail to induce leukemia upon transplantation into irradiated recipients following transduction with an AML1-ETO9a retrovirus. These data highlight disruption of the Myb-p300 interaction as a potential therapeutic strategy for AML and suggest that such a strategy would have a useable therapeutic index since Booreana mice, unlike Myb null mice, are viable. Finally we have begun to explore the molecular basis of the these observations by gene expression profiling; this highlighted several genes previously implicated in myeloid leukemogenesis as being differentially expressed between WT and Booreana cells transduced with AML1-ETO9a.
Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes.
Specimen part
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