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GSE18446
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
- 4 Downloadable Samples
Description
Analysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.
Publication Title
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
Description
Both bone morphogenetic proteins (BMPs) and histone deacetylases (HDACs) have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and trichostatin A (TSA)-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis.
Publication Title
Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Xenopus laevis, Mus musculus
- 5 Downloadable Samples
Description
Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones.
Publication Title
Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.
Publication Title
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 46 Downloadable Samples
Description
Immune deficiency is common in cancer, but the biological basis for this and ways to reverse it remains elusive. Here we present a mouse model of B cell chronic lymphocytic leukemia (CLL) that recapitulates changes in the non-malignant circulating T cells seen in patients with this illness.1 To validate this model, we examined changes in T cell gene expression, protein expression and function in Em-TCL1 transgenic mice as they developed CLL 2,3 and demonstrate that development of CLL in these transgenic mice is associated with changes in impaired T cell function and in gene expression in CD4 and CD8 T cells similar to those observed in patients with this disease. Infusion of CLL cells into non-leukemia bearing Em-TCL1 mice rapidly induces these changes, demonstrating a causal relationship between leukemia and the induction of T cell changes. This model allows dissection of the molecular changes induced in CD4 and CD8 T cells by interaction with leukemia cells and further supports the concept that cancer results in complex abnormalities in the immune microenvironment.
Publication Title
E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 33 Downloadable Samples
Description
The mature CNS contains PDGFRA+ oligodendrocyte progenitor cells (OPC) which may remain quiescent, proliferate, or differentiate into oligodendrocytes. In human gliomas, rapidly proliferating Olig2+ cells resembling OPCs are frequently observed. We sought to identify, in vivo, candidate pathways uniquely required for OPC differentiation or quiescence. Using the bacTRAP methodology, we generated and analyzed mouse lines for translational profiling the major cells types (including OPCs), in the normal mouse brain. We then profiled oligodendoglial (Olig2+) cells from a mouse model of Pdgf-driven glioma. This analysis confirmed that Olig2+ tumor cells are most similar to OPCs, yet, it identified differences in key progenitor genes - candidates for promotion of differentiation or quiescence.
Publication Title
Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin
Publication Title
Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
Description
Susceptible and Resistant mouse strain, e.g. DBA/2J and C57BL/6J respectively, were inoculated with a highly pathogenic H5N1 influenza A virus (A/Hong Kong/213/2003) for 72 hours.
Publication Title
Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 7 Downloadable Samples
Description
Repair of injured muscle involves repair of injured myofibers through the involvement of dysferlin and its interacting partners, including annexin. Studies with mice and patients have established that dysferlin deficit leads to chronic inflammation and adipogenic replacement of the diseased muscle. However, longitudinal analysis of annexin deficit on muscle pathology and function is lacking. Here we show that unlike annexin A1, but similar to dysferlin, lack of annexin A2 (AnxA2) causes poor myofiber repair and progressive weakening with age. However, unlike dysferlin-deficient muscle, AnxA2-deficient muscles do not exhibit chronic inflammation or adipogenic replacement. Deletion of AnxA2 in dysferlin deficient mice reduces inflammation, adipogenic replacement, and loss in muscle function caused by dysferlin deficit. These results show that: a) AnxA2 facilitates myofiber repair, b) chronic inflammation and adipogenic replacement of dysferlinopathic muscle requires AnxA2, and c) inhibiting AnxA2-mediated inflammation is a novel therapeutic avenue for dysferlinopathy.
Publication Title
Annexin A2 links poor myofiber repair with inflammation and adipogenic replacement of the injured muscle.
Sample Metadata Fields
Age, Specimen part
View Samples