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GSE37286
Mus musculus
34 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase inhibitor lonafarnib and the tyrosine kinase inhibitor nilotinib. This results in an initial large reduction in cell viability of the culture and inhibition of cell proliferation. However, after a number of days, cell death ceases and the culture becomes drug-tolerant, enabling cell division to resume. We used gene expression profiling to analyze changes in the transcriptome of these leukemia cells over a 3-4 week period, taking samples at the start, the point at which most of the leukemia cells had been eradicated while a small percentage survived, and at the end when the cells were proliferating again.
Publication Title
Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs.
Publication Title
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Primary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling.
Publication Title
Murine models of IDH-wild-type glioblastoma exhibit spatial segregation of tumor initiation and manifestation during evolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In gastrulation, distinct progenitor cell populations are induced and sorted into the three germ layers ectoderm, mesoderm and endoderm. In order to identify genes involved in germ layer specification and morphogenesis, we identified genes differentially expressed between ectodermal and mesendodermal progenitor cells. To do so, we first generated highly enriched pools of ectodermal and mesendodermal progenitor cells. Mesendodermal cells were generated by over-expressing the Nodal signal Cyclops in wild type embryos and ectodermal cells were taken from mz-one-eyed-pinhead (oep) mutant embryos. We then compared the transcriptome of ectodermal versus mesendodermal cells taken from embryos at 7 hours post fertilization (hpf). In wild type embryos at this stage (70% epiboly), the first ectodermal and mesendodermal progenitor cells have already been sorted into their respective germ layers and ingression of mesendodermal progenitors is still ongoing.
Publication Title
Identification of regulators of germ layer morphogenesis using proteomics in zebrafish.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4.
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4. Overall design: ES cells and cardiomyocytes with Hey1 or Hey2 overexpression were compared to control cells
Publication Title
Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Affymetrix gene expression AID-GFP-positive vs AID-GFP-negative
Publication Title
The B cell mutator AID promotes B lymphoid blast crisis and drug resistance in chronic myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Publication Title
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Interleukin-1 receptor associated kinase 1 (IRAK1) is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation. Here, we show that IRAK1 promotes Th17 development by mediating IL-1 induced upregulation of IL-23R and subsequent STAT3 phosphorylation, thus enabling sustained IL-17 production. Moreover, we show that IRAK1 signaling fosters Th1 differentiation by mediating T-bet induction and counteracts Treg generation. Cotransfer experiments revealed that Irak1-deficient CD4+ T cells have a cell-intrinsic defect in generating Th1 and Th17 cells under inflammatory conditions in spleen, mesenteric lymph nodes and colon tissue. Furthermore, IRAK1 expression in T cells was shown to be essential for T cell accumulation in the inflamed intestine and mLNs. Transcriptome analysis ex vivo revealed that IRAK1 promotes T cell activation and induction of gut-homing molecules in a cell-intrinsic manner. Accordingly, Irak1-deficient T cells failed to upregulate surface expression of 47 integrin after transfer into Rag1-/- mice and their ability to induce colitis was greatly impaired. Lack of IRAK1 in recipient mice provided additional protection from colitis. Therefore, IRAK1 plays an important role in intestinal inflammation by mediating T cell activation, differentiation and their accumulation in the gut. Thus, IRAK1 is a promising novel target for therapy of inflammatory bowel diseases.
Publication Title
IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity.
Sample Metadata Fields
No sample metadata fields
View Samples