Filters
Technology
Platform
GSE19684
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The morphogen and mitogen, Sonic Hedgehog, activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of nave mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development.
Publication Title
Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Myc-driven Group 3 medulloblastoma (MB) is the most aggressive tumor among the four subgroups classified by transcriptome, genomic landscape and clinical outcomes. So far in all available mouse Group 3 models, the constitutive ectopic Myc expression was under control of LTR element or other exogenous promoters within the vectors, which were randomly inserted into the genome with multiple copies. Here we are deploying nuclease deficient CRISPR/dCas9-based transactivator that is targeted to promoter DNA sequences by specific guide RNA to force the transcriptional activation of endogenous Myc in p53-/-;cdkn2c-/- neurospheres cells. A combination of three sgRNAs together with dCas9-VP64 induced the highest expression of endogenous Myc. When the targeted cells were transplanted to the cortex of recipients, tumors arose fully recapitulate the Group 3 MB in human. This novel mouse model should significantly strengthen our understanding and treatment of the Myc-driven Group 3 medulloblastoma.
Publication Title
Mouse medulloblastoma driven by CRISPR activation of cellular Myc.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Aortic valve regurgitation (AR) imposes a severe volume overload to the left ventricle (LV) which results in dilation, eccentric hypertrophy and eventually loss of function. Little is known about the impact of AR on LV gene expression. We therefore conducted a gene expression profiling study in the LV of male Wistar rats with chronic (9 months) and severe AR.
Publication Title
Multiple short-chain dehydrogenases/reductases are regulated in pathological cardiac hypertrophy.
Sample Metadata Fields
Sex
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Tissue morphogenesis relies on proper differentiation of morphogenetic domains, adopting specific cell behaviours. Yet, how signalling pathways interact to determine and coordinate these domains remains poorly understood. Dorsal closure (DC) of the Drosophila embryo represents a powerful model to study epithelial cell sheet sealing. In this process, JNK (JUN N-terminal Kinase) signalling controls leading edge (LE) differentiation generating local forces and cell shape changes essential for DC. The LE represents a key morphogenetic domain in which, in addition to JNK, a number of signalling pathways converges and interacts (anterior/posterior -AP- determination; segmentation genes, such as Wnt/Wingless; TGF/Decapentaplegic). To better characterize properties of the LE morphogenetic domain, we used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo.
Publication Title
The Drosophila serine protease homologue Scarface regulates JNK signalling in a negative-feedback loop during epithelial morphogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Publication Title
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 49 Downloadable Samples
Illumina HiSeq 2000
Description
We previoiusly identified WDR11 as a potential tumor suppressor in murine medulloblastoma models. To determine additional genes/pathways affected by WDR11 overexpression.To compare somatic mutations of murine models with human medulloblastoma (MB), we performed whole-exome sequencing of mouse tumors representing three distinct MB subgroups: Wnt, Sonic Hedgehog (Shh) and Group 3 (G3). 64 somatic mutations were identified and validated, including 40 predicted to cause amino acid changes. After filtering and cross-species analysis with 366 human MBs from four independent studies, human orthologs for 16 of the 40 mouse genes were found to harbor non-silent mutations in human MB. Loss-of-function Mll2 mutations detected in one mouse tumor were previously reported in 30 of 366 human MBs. In mice with G3 MB, one mouse that died at least 15 days earlier than the others had four novel candidate genes harboring non-silent somatic mutations, Lrfn2, Smyd1, Ubn2 and Wdr11. To test whether these genes had tumor suppressive activity, we constitutively overexpressed each wild type gene in murine G3 tumorspheres followed by intracranial implantation. Mice harboring mouse G3 MB overexpressing WDR11 showed extended survival compared to the other three genes. Genes in the KEGG WNT signaling pathway, including Ccnd1/2/3, Myc and Tcf7l1, were down-regulated in G3 MB tumorspheres overexpressing WDR11, consistent with reduced tumor progression. In conclusion, we demonstrated that common spontaneous mutations were shared between human and murine models of MB suggesting similar molecular mechanisms of tumorigenesis, and identified WDR11 as a protein with tumor suppressive activity in G3 MB. Overall design: Compare differentially expressed genes in WDR11 overexpression group versus control group.
Publication Title
Exome sequencing analysis of murine medulloblastoma models identifies WDR11 as a potential tumor suppressor in Group 3 tumors.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
ZBTB4 is a mammalian transcription factor with Zinc fingers and a BTB/POZ domain, which can bind methylated CpGs, as well as certain unmethylated consensus sequences. ZBTB4 is frequently downregulated in human cancers, but it is unclear whether this is a cause or consequence of transformation. To investigate the role of ZBTB4 in normal and pathological conditions, we generated Zbtb4-/- mice
Publication Title
Loss of the Methyl-CpG-Binding Protein ZBTB4 Alters Mitotic Checkpoint, Increases Aneuploidy, and Promotes Tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To understand the underlying cause for the observed apoptosis in E2f1-3 deficient myeloid cells. We compared gene expression profiles of Cd11b+ sorted myeloid cells isolated from bone marrow of control (E2F1-/- ) and experimental (Mxcre;E2F1-/-2-/-3f/f ) mice.
Publication Title
E2f1-3 are critical for myeloid development.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a progenitor cells gene expression program, while priming a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdts first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
No sample metadata fields
View Samples