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Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Comparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of MSI2 in vivo
Publication Title
Transformation of the intestinal epithelium by the MSI2 RNA-binding protein.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoietic stem and progenitor cells (Lineagelo ScaI+ c-Kit+) were sorted 4 weeks post pIpC injection. RNA was extracted using TRIZOL and RNEASY RNA extraction kit. RNA was then amplified using NUGEN Pico amplification kit, fragmented and hybridized on Mouse Expression Array 430 2.0. Signal normalization was performed by RMA method. Data were analyzed using GSEA across the complete list of genes ranked by signal-to-noise ratio.
Publication Title
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Leukemia stem cells (LSCs) are found in most aggressive myeloid diseases and contribute to therapeutic resistance. Genetic and epigenetic alterations cause a dysregulated developmental program in leukemia. The MSI2 RNA binding protein has been previously shown to predict poor survival in leukemia. We demonstrate that the conditional deletion of Msi2 results in delayed leukemogenesis, reduced disease burden and a loss of LSC function. Gene expression profiling of the Msi2 ablated LSCs demonstrates a loss of the HSC/LSC and an increase in the differentiation program. The gene signature from the Msi2 deleted LSCs correlates with survival in AML patients. MSI2’s maintains the MLL self-renewal program by interacting with and retaining efficient translation of Hoxa9, Myc and Ikzf2. We further demonstrate that shRNA depletion of the MLL target gene Ikzf2 also contributes to MLL leukemia cell survival. Our data provides evidence that MSI2 controls efficient translation of the oncogenic LSC self-renewal program and a rationale for clinically targeting MSI2 in myeloid leukemia. Overall design: RNA-Seq was performed on sorted c-Kit high leukemic cells from 2 Msi2 -/- and 2 Msi2 f/f mice.
Publication Title
Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSC), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of Msi2 in a mouse model increases HSC cell cycle progression and cooperates with BCR-ABL1 to induce an aggressive leukemia. MSI2 is over-expressed in human myeloid leukemia, and expression levels directly correlate with decreased patient survival, thereby defining MSI2 expression as a novel prognostic marker in acute myeloid leukemia (AML). Depletion of MSI2 in human myeloid leukemia cells leads to decreased proliferation and apoptosis. These data implicate the MSI2 RNA binding protein in myeloid leukemogenesis and identify a novel potential target for therapy in AML.
Publication Title
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
Sample Metadata Fields
Specimen part
View Samples
GSE74321- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Comparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of Msi1 in vivo
Publication Title
The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Analysis of musashi2 contribution towards maintaing myelodysplastic phenotype in stem cells. We find that musashi2 plays an integral role in maintaining the myelodysplastic phenotype Overall design: Control, NUP98-HOXD13; NHD13, NHD13/MSI2 bone marrow was transplated allowed to engraft into lethally irradiated congenic CD45.1 animals. Mice were then fed doxycycline to induce MSI2 overexpression. Mice were induced for 3 months and then CD45.2 Lineage lo Sca1+ and Kit+ cells were sorted and then assessed for gene expression.
Publication Title
MSI2 is required for maintaining activated myelodysplastic syndrome stem cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Due to the urgent need of new targeting strategies in PCa, AR interacting proteins should be considered. In this study we aimed to test the effect of a long-term knockdown of NCOA1, an AR coactivator, in PCa progression and metastatogenesis and whether NCOA1 could be used as a possible therapeutic target. To test the consequences of NCOA1 knockdown on proliferation, we performed by 3H thymidine incorporation assays revealing a strong reduction in castration resistant MDA PCa 2b and androgen-dependent LNCaP cells, without affecting AR negative PC3 cells. Furthermore, Boyden chamber assays revealed a strong decrease in migration and invasion upon NCOA1 knockdown. Using a cDNA microarray, we identified protein kinase D1 (PRKD1) as one prominent upregulated gene in MDA PCa 2b, which was not seen in PC3 cells. Knockdown of PRKD1 clearly reverted the reduced migratory potential. Moreover, we found phospholipase A2, group7 (PLA2G7) and eukaryotic translation initiation factor 5A2 (EIF5A2), which might be involved in migration of PC3 cells. Further, we can clearly demonstrate that PRKD1 is negatively regulated by the AR/NCOA1 complex. In addition, immunhistochemical staining revealed a strong increase in NCOA1 expression in matched and unmatched patients samples, respectively between normal prostate and primary tumor. Regarding the PRKD1 staining, no final conclusion can be drawn in terms of a tumor suppressor function. Thus, our findings directly associate NCOA1/AR complex with PRKD1 regulation and further suggest NCOA1 as a potential therapeutic target also due to the effect on PC3 cell migration.
Publication Title
The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.
Publication Title
In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In order to investigate the function of Bach2 in pre-B ALL, we isolated bone marrow cells from wildtype and Bach2 knockout mice of C57Bl6 background and transformed them with BCR-ABL1.
Publication Title
Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Treatment
View Samples