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GSE110932
Mus musculus
12 Downloadable Samples
Description
The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location since SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high level SHH signaling compared to GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide new insights into intrinsic differences within GCPs that impact on SHH-MB progression.
Publication Title
Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.
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Specimen part
View Samples- Mus musculus
- 116 Downloadable Samples
Description
The gastrointestinal (GI) tract can have significant impact on the regulation of the whole body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analyses in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, both obese mouse groups had significant amount of gene expression changes in the stomach (ob/ob: 959; HFD: 542), much more than the number of changes in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes and insulin resistance. In addition, the gene expression profile strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity.
Publication Title
Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.
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Specimen part
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.
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Specimen part
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.
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Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
miR-155 transgenic mice develop pre-B cell leukemia/lymphoma. Though some targets of miR-155 are known, understanding of the mechanism by which miR-155 overexpression drives malignant transformation is not known. MicroRNAs regulate multiple genes.
Publication Title
miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eμ-miR-155 transgenic mouse model.
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Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
EphB receptors regulate the proliferation and positioning of intestinal stem and progenitor cells. In addition, they can act as tumor promoters for adenoma development, but suppress progression to invasive carcinoma. Here we used imatinib to abrogate Abl kinase activity in ApcMin/+ mice and in mice with LGR5+ stem cells genetically targeted for APC. This treatment inhibited the tumor-promoting effects of EphB signaling without attenuating EphB-mediated tumor suppression, demonstrating the role of EphB signaling in intestinal tumor initiation. The investigated treatment regimen extended the lifespan of ApcMin/+ mice, and reduced cell proliferation in cultured slices of adenomas from FAP patients. These findings connect the EphB signaling pathway to the regulation of intestinal adenoma initiation via Abl kinase. Our findings may have clinical implications for pharmacological therapy against adenoma formation and cancer progression in patients predisposed to develop colon cancer.
Publication Title
An EphB-Abl signaling pathway is associated with intestinal tumor initiation and growth.
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Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Androgenetic haploid embryonic stem cells produce live transgenic mice.
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Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 21 Downloadable Samples
Description
Haploid stem cells offer an easy-to-manipulate genetic system and therefore have great values for studies of recessive phenotypes. Here, we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ-layers in vitro and in vivo, and contribute to germline of chimeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte injection procedure can also produce viable transgenic mice from genetically engineered ahES cells.
Publication Title
Androgenetic haploid embryonic stem cells produce live transgenic mice.
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Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Haploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. Here, we report that mouse haESCs can differentiate in vitro into haploid epiblast stem cells (haEpiSCs), which maintain an intact haploid genome, unlimited self-renewal potential, and durable pluripotency to differentiate into various tissues in vitro and in vivo. Mechanistically, the maintenance of self-renewal potential depends on the Activin/bFGF pathway. We further show that haEpiSCs can differentiate in vitro into haploid progenitor-like cells.
Publication Title
Durable pluripotency and haploidy in epiblast stem cells derived from haploid embryonic stem cells in vitro.
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Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Rb and E2F are thought to play antagonistic roles in celll proliferation. However, this model is based mostly from in vitro cell culture systems. We used small intestines to test this model in vivo.
Publication Title
E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells.
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Sample Metadata Fields
Age, Specimen part
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