Analysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Specimen part
View SamplesLineage negativ Sca1+ Kit+ bone marrow cells (containing putative hematopoietic stem cells) subfractionation based on CD34 and FLT3 identifies three functionally destinc subpopulations (LSKCD34-FLT3-, LSKCD34+FLT3- & LSKCD34+FLT3+).
Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.
No sample metadata fields
View SamplesComparison of gene expression in intestinal epithelial cells in the presence or absence of ectopic induction of MSI2 in vivo
Transformation of the intestinal epithelium by the MSI2 RNA-binding protein.
Specimen part
View SamplesHematopoietic 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.
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs.
Specimen part
View SamplesFLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors
FLT3-ITDs instruct a myeloid differentiation and transformation bias in lymphomyeloid multipotent progenitors.
Sex, Specimen part
View SamplesGene expression analysis of purified endothelial cells (Ecs), mesenchymal stem cells (MSCs) and mononuclear cells (MNCs) from wild-type and Flt3-ITD knock-in mice. Overall design: Differentially expressed genes analysis of haematopoietic and niche cell populations from Flt3-ITD mice
Niche-mediated depletion of the normal hematopoietic stem cell reservoir by Flt3-ITD-induced myeloproliferation.
No sample metadata fields
View SamplesLeukemia 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.
Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.
No sample metadata fields
View SamplesAn immune-restricted lymphomyeloid-primed progenitor with the capacity to contribute to both myeloid and lymphoid lineages in the developing embryo emerges prior to definitive HSCs. Overall design: Examination of fetal sorted lymphoid primed progentors and adult progenitors The fastq files are not provided at this time due to further analyses.
Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells.
No sample metadata fields
View SamplesDue 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.
The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia.
Specimen part, Cell line, Treatment
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