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GSE10167
Mus musculus
6 Downloadable Samples
Description
The object of this study was to identify genes transcriptionally upregulated and downregulated in response to Tcof1 haploin-sufficiency during mouse embryogensis
Publication Title
Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The biology of chronic myeloid leukemia (CML)-stem cells is still incompletely understood. Therefore, we previously developed an inducible transgenic mouse model in which stem cell targeted induction of BCR-ABL expression leads to chronic phase CML-like disease. Here, we now demonstrate that the disease is transplantable using BCR-ABL positive LSK cells (lin-Sca-1+c-kit+). Interestingly, the phenotype is enhanced when unfractionated bone marrow (BM) cells are transplanted. However, neither progenitor cells (lin-Sca-1-c-kit+) nor mature granulocytes (CD11b+Gr-1+), or potential stem cell niche cells were able to transmit the disease or alter the phenotype. The phenotype was largely independent of BCR ABL priming prior to transplant. However, BCR-ABL abrogated the potential of LSK cells to induce full blown disease in secondary recipients. Subsequently, we found that BCR-ABL increased the fraction of multipotent progenitor cells (MPP) at the expense of long term HSC (LT-HSC) in the BM. Microarray analyses of LSK cells revealed that BCR-ABL alters the expression of genes involved in proliferation, survival, and hematopoietic development. Our results suggest that BCR-ABL induces differentiation of LT-HSC and decreases their self renewal capacity. Furthermore, reversion of BCR-ABL eradicates mature cells while leukemic stem cells persist, giving rise to relapsed CML upon re-induction of BCR-ABL.
Publication Title
BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
Description
Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain.
Publication Title
Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A mouse model of the most aggressive subgroup of human medulloblastoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Description
Mouse models of medulloblastoma are compared to human subgroups through microarray expression and other measures
Publication Title
A mouse model of the most aggressive subgroup of human medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
The ACBP knockout were created by targeted disruption of the gene in mice. The expression profiling was performed on liver tissue from ACBP-/- (KO) and +/+ (WT) mice at the age of 21 days, which in our study is the time immediately before weaning. The mice used for this experiment were taken directly away from their mother. Thus, having free access to chow and breast milk until sacrificed at 8-11am
Publication Title
Disruption of the acyl-CoA-binding protein gene delays hepatic adaptation to metabolic changes at weaning.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 43 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 56 Downloadable Samples
Description
Mice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.
Publication Title
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 43 Downloadable Samples
Description
Mice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.
Publication Title
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 22 Downloadable Samples
Description
Genomic technologies have unmasked molecularly distinct subgroups among tumors of the same histological type; but understanding the biologic basis of these subgroups has proved difficult since their defining alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher complex genomic data sets by matching the genetic alterations contained within these, with candidate cells of origin, to generate accurate disease models. Using an integrated genomic analysis we first identified subgroups of human ependymoma: a form of neural tumor that arises throughout the central nervous system (CNS). Validated alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. Matching the transcriptomes of human ependymoma subgroups to those of distinct types of mouse radial glia (RG)neural stem cells (NSCs) that we identified previously to be a candidate cell of origin of ependymoma - allowed us to select RG types most likely to represent cells of origin of disease subgroups. The transcriptome of human cerebral ependymomas that amplify EPHB2 and delete INK4A/ARF matched most closely that of embryonic cerebral Ink4a/Arf-/- RG: remarkably, activation of EphB2 signaling in this RG type, but not others, generated highly penetrant ependymomas that modeled accurately the histology and transcriptome of one human cerebral tumor subgroup (subgroup D). Further comparative genomic analysis revealed selective alterations in the copy number and expression of genes that regulate neural differentiation, particularly synaptogenesis, in both mouse and human subgroup D ependymomas; pinpointing this pathway as a previously unknown target of ependymoma tumorigenesis. Our data demonstrate the power of comparative genomics to sift complex genetic data sets to identify key molecular alterations in cancer subgroups.
Publication Title
Cross-species genomics matches driver mutations and cell compartments to model ependymoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples