Understanding the role of EZH2 insufficiency in the pathogenesis of PMF
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Goro Sashida
PROVIDER: E-GEOD-69500 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Loss-of-function mutations in EZH2 are associated with worse outcomes in patients with primary myelofibrosis (PMF). To understand how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for Ezh2 conditional deletion and a JAK2V617F transgene. The total bone marrow cells isolated from Cre-ERT2, Ezh2flox/flox;Cre-ERT2, JAK2V617F;Cre-ERT2 and JAK2V617F;Ezh2flox/flox;Cre-ERT2 mice were transplanted into lethally irradiated CD45.1+ wild-type recipient mice. As we deleted Ezh2 at four weeks post transplantation, we performed gene-expression analysis of LSKs and MEPs isolated from the recipient mice at 2 months post transplantation.
2015-06-04 | E-GEOD-69498 | biostudies-arrayexpress
Project description:Loss-of-function mutations in EZH2 are associated with worse outcomes in patients with primary myelofibrosis (PMF). To understand how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for Ezh2 conditional deletion and a JAK2V617F transgene. The total bone marrow cells isolated from JAK2V617F;Ezh2flox/flox;Cre-ERT2 mice were transplanted into lethally irradiated CD45.1+ wild-type recipient mice. Post the deletion of Ezh2, we administered JAK2V617F/Ezh2?/? mice with JQ1 or control DMSO for two weeks, and performed gene-expression analysis of bone marrow LSKs and MEPs immediately after completion of JQ1 treatment.
2015-06-04 | E-GEOD-69499 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-06-04 | GSE69500 | GEO
Project description:Recent studies have showed that loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2, are often associated with RUNX1 mutations in myelodysplastic syndrome (MDS) patients. We established a novel MDS model mouse by transducing a RUNX1S291fs mutant in hematopoietic stem cells followed by deletion of Ezh2 and found that Ezh2 loss significantly promoted RUNX1S291fs-induced MDS. We retrovirally transduced RUNX1S291fs or empty-control into either Cre-ERT;Ezh2wt/wt or Cre-ERT;Ezh2flox/flox (CD45.2+) HSCs. The transduced cells were transplanted into lethally irradiated recipient mice together with life-saving CD45.1+ wild-type bone marrow cells. After deletion of Ezh2, gene expression analysis were performed on pooled bone marrow LSK cells isolated from WT, Ezh2Δ/Δ, RUNX1S291fs, and RUNX1S291fs/Ezh2Δ/Δ mice (n=2-4) and two distinct RUNX1S291fs/Ezh2Δ/Δ-MDS mouse.
2013-09-04 | E-GEOD-50537 | biostudies-arrayexpress
Project description:Understanding the role of EZH2 insufficiency in the pathogenesis of PMF
| PRJNA285739 | ENA
Project description:Cell differentiation and proliferation are mutually exclusive. Although differentiating neurons are recognized as post-mitotic non-dividing cells, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons proliferate and form tumor. Here, we found that the acute inactivation of all Rb family in differentiating cortical excitatory neurons caused radial migration defect and S-phase progression but not cell division, whereas that in cortical progenitors caused the cell division of the differentiating neurons generated from Rb â??/â??; p107 â??/â??; p130 â??/â?? (Rb-TKO) progenitors. Genome-wide DNA methylation analysis revealed that proximal promoters tended to become methylated during differentiation in vivo. DNA demethylation by DNA methyltransferase inhibitor allowed the acutely inactivated Rb-TKO differentiating neurons to undergo G2/M-phase progression. Our finding illustrate that cortical excitatory neurons epigenetically lose their proliferative potency after neurogenesis. 4 samples of the V/SVZ (ventricular/subventricular zone) tissue and 4 samples of the CP (cortical plate) tissue
2016-07-03 | E-GEOD-37576 | biostudies-arrayexpress
Project description:Recent studies have shown that multiple components of the mRNA splicing machinery are mutated in myelodysplastic syndrome (MDS) patients. SF3B1 is frequently mutated in refractory anemia with ringed sideroblasts (RARS)-MDS patients, however, the pathophysiological role of SF3B1 mutations has not been elucidated yet. In this study, we examined the function of Sf3b1 in murine hematopoiesis. Since Sf3b1 null homozygotes died during preimplantation development, in this study, we utilized Sf3b1 heterozygous mice showing grossly normal growth. We harvested bone marrow stem/progenitor (LSK) cells from wild type (WT) and Sf3b1+/- mice (n=4) at 20 weeks old. In addition, to exclude the possibility of indirect effect from bone marrow environment, we transplanted total bone marrow cells from WT or Sf3b1+/- (CD45.2+) mice into lethally irradiated CD45.1+ recipient mice, and then harvested (CD45.2+) LSK cells from the recipients (n=5) at 9 months-post transplantation.
2013-09-20 | E-GEOD-51038 | biostudies-arrayexpress
Project description:Loss of polycomb-group gene Ezh2 causes activation of fetal gene signature in adult mouse bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). Ezh2 directly represses fetal-specific let-7 target genes, including Lin28, thereby cooperates with let-7 microRNAs in silencing fetal gene signature in BM HSPCs. We purified Lineage-Sca-1+c-Kit+ (LSK) HSPCs from E14.5 FL and adult BM and subjected them to microarray analysis.
2015-08-27 | E-GEOD-69760 | biostudies-arrayexpress
Project description:Cell cycle deregulation leads to abnormal proliferation and cell death in a context-specific manner. Cell cycle progression driven via Rb pathway forces neurons to undergo S-phase, resulting in cell death associated with the progression of neuronal degeneration. Nevertheless, some Rb- and Rb family (Rb, p107, and p130)-deficient differentiating neurons can proliferate and form tumors. Here, we found that differentiating cerebral cortical excitatory neurons underwent S-phase progression but not cell division after acute Rb family inactivation in differentiating neurons. However, the differentiating neurons underwent cell division and form tumors when Rb family members were inactivated in cortical progenitors. Differentiating neurons generated from Rb -/-; p107 -/-; p130 -/- (Rb-TKO) progenitors, but not acutely inactivated Rb-TKO differentiating neurons, activated DNA double-strand break (DSB) repair pathway without increasing the tri-methylation of histone H4 at lysine 20 (H4K20M3), which is known to protect from DNA damage. The activation of DSB repair pathway was essential for the cell division of Rb-TKO differentiating neurons. These results suggest that newly-born cortical neurons from progenitors epigenetically become protected from DNA damage and cell division in a Rb family-dependent manner. 3 samples of pCAG-control, pCAG-RbTKO, pMAP2-control, and pMAP2-RbTKO cells
2014-01-01 | E-GEOD-37577 | biostudies-arrayexpress
Project description:Objective: To evaluate gene expression profiles in multiple sclerosis (MS) patients who improved their fatigue status after a program of physical exercise and to compare them with healthy controls (HC). Methods: A prospective longitudinal study was conducted. Gene expression in whole blood was profiled at baseline in 7 healthy controls and also in 7 fatigued-MS patients. Patients underwent a physical exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed at the end of this program. Results: MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with healthy controls. Fatigue improved at the end of the physical activity program, and, in parallel, systemic activation of interferon related genes disappeared. Conclusions: Fatigue improvement following an exercise program is associated to down modulation of interferon activity at the systemic level in MS patients. Our results provide a biological basis for the observed benefit of physical exercise in MS.
2015-09-27 | E-MTAB-2973 | biostudies-arrayexpress