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E-GEOD-32425
Danio rerio
1 Downloadable Sample
Description
Fluorescent-labeled zebrafish RAS-induced embryonal rhabdomyosarcoma (ERMS) were created to facilitate in vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in diverse cellular compartments. Using this strategy, we have identified a molecularly distinct ERMS cell subpopulation that expresses high levels of myf5 and is enriched for ERMS-propagating potential when compared with other tumor-derived cells. Embryonal rhabdomyosarcoma (ERMS) is an aggressive pediatric sarcoma of muscle. Here, we show that tumor-propagating potential is confined to myf5+ERMS cells and can be visualized in live, fluorescent transgenic zebrafish. During early tumor growth, myf5+ERMS cells reside within an expanded satellite cell compartment, but by late stage ERMS, myf5+cells are dynamically reorganized into distinct regions separated from differentiated tumor cells. Human ERMS also contain distinct areas of differentiated and undifferentiated cells. Time-lapse imaging revealed that myf5+ERMS cells populate newly formed tumor only after seeding by highly migratory myogenin+ ERMS cells. This finding helps explain the clinical observation that Myogenin positivity correlates with poor clinical outcome in human ERMS and suggests that differentiated tumor cells play critical roles in metastasis. One-cell stage myf5-GFP/mylz2-mCherry fluorescent transgenic zebrafish were injected with rag2-kRAS12D. A subset of animals developed ERMS. Tumor cells were transplanted into syngeneic recipient animals that lacked fluorescent reporter expression. ERMS cell subfractions were isolated from transplant animals and purified cell populations obtained following two rounds of FACS. Sorted cells were 1) analyzed by microarray/RT-PCR and 2) transplanted at limiting dilution into syngeneic animals. These experiments confirm that zebrafish ERMS contain molecularly distinct cell subfractions that express high levels of myf5-GFP and exhibit difference in gene expression when compared to other ERMS cell subtypes. All four fluorescent-labeled cell populations were analyzed (n=2 tumors total).
Publication Title
In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Efficient and sustained knockdown of DNMT1 transcript and protein was achieved using a consecutive transfection protocol in the mouse pituitary adenoma cell line, AtT-20. Genome wide microarray analysis identified 91 transcripts that were significantly differentially expressed relative to cells treated with a non-targeting control.
Publication Title
Genome-wide analysis in a murine Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
BACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
Publication Title
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Increasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
Publication Title
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 26 Downloadable Samples
Description
The transcription factor Nkx2.5 is required for specification of pharyngeal arch second heart field (SHF) progenitors that contribute to outflow tract (OFT) and right ventricle (RV) formation. Multiple sets of microarray data were analyzed to identify genes that are candidate targets of Nkx2.5 in the second heart field. These sets are: 1) publicly available data for cardiothoracic tissue from E9.5 Nkx2.5 wild-type, heterozygous and homozygous embryos; 2) an analysis of mouse E10.5 pharyngeal arch tissue; 3) an analysis of mouse E12.5 heart tissue; and 4) a temporal analysis of the cardiogenic cell line P19CL6. This combined analysis identified 11 genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF-containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5 expression.
Publication Title
Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
Description
Pluripotent P19CL6 embryonic carcinoma cells can be differentiated to a cardiac lineage by culture in the presence of DMSO. The goal of this study was to characterize temporal gene expression patterns associated with cardiogenic differentiation. Gene expression analysis was conducted on differentiating P19CL6 cells at several time points following induction with 1% DMSO. Samples were processed for analysis by Affymetrix GeneChip.
Publication Title
Jarid2 is among a set of genes differentially regulated by Nkx2.5 during outflow tract morphogenesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Obesity is often associated with a low-grade systemic inflammation state that contributes to the development of insulin resistance and atherosclerotic complications. This is usually coupled with increased macrophage infiltration in the adipose tissue and a defect in adipocyte differentiation that results in accumulation of hypertrophic fat cells characterized by a deregulated pattern of adipokine expression. Here we show that knockdown of histone demethylase lsd1 in 3T3-L1 preadipocytes results in defective adipogenesis and derepression of an inflammatory program in these cells.
Publication Title
Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Description
T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection.
Publication Title
PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
Dysregulated Wnt signalling is seen in approximately 30% of hepatocellular cancers, thus finding pathways downstream of activation of Wnt signalling is key. Using cre lox technology we have deleted the the adenomatous polyposis coli tumour suppressor protein (Apc) within the adult mouse liver and observed a rapid increase in nuclear beta-catenin and C-Myc. This is associated with an induction of proliferation leading to hepatomegally within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes we analysed the impact of inactivating Apc in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegally phenotypes following Apc loss. However c-Myc deletion, which rescues the phenotypes of Apc loss in the intestine, had no effect on the phenotypes of Apc loss. The consequences of deregulation the Wnt pathway within the liver are therefore strikingly different to those observed within the intestine, with the vast majority of Wnt targets beta-catenin dependent but c-Myc independent in the liver.
Publication Title
B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
We are investigating hepatic transcriptional responses associated with castration and tumorigenic hepatitis induced by Helicobacter hepaticus infection in mature male A/JCr mice
Publication Title
Hepatocellular carcinoma associated with liver-gender disruption in male mice.
Sample Metadata Fields
No sample metadata fields
View Samples