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Expression data from loss-of-TET2 and/or JAK2V617F mutant Lineage-c-Kit+Sca-1+ (LSK) bone marrow cells

ABSTRACT: Recent studies have shown that both TET2 mutation and JAK2V617F mutation are frequent in myeloproliferative neoplasms patients. The pathophysiological roles of each mutation have been elucidated in murine models, but the cooperative effect of the two mutations has not been elucidated yet. In this study, we examined the function of the cooperative effect of loss-of-TET2 function and JAK2V617F mutation in murine hematopoiesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE62302 | GEO | 2014/10/16

SECONDARY ACCESSION(S): PRJNA263920

REPOSITORIES: GEO

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Expression data from loss-of-TET2 and/or JAK2V617F mutant Lineage-c-Kit+Sca-1+ (LSK) bone marrow cells

Project description:Recent studies have shown that both TET2 mutation and JAK2V617F mutation are frequent in myeloproliferative neoplasms patients. The pathophysiological roles of each mutation have been elucidated in murine models, but the cooperative effect of the two mutations has not been elucidated yet. In this study, we examined the function of the cooperative effect of loss-of-TET2 function and JAK2V617F mutation in murine hematopoiesis. In this study, we utilized wild type (WT) mice, TET2 knock down (TET2KD) mice, JAK2V617F transgenic mice, double mutant mice. We transplanted 4 types of E14.5 fetal liver cells (WT, TET2KD, JAK2V617F, double mutant) into lethally irradiated mice. At 10-16 weeks post-transplantation, LSK cells from the BM of the recipients were collected, and gene expression analysis was performed. (WT,5 mice at 16 weeks; TET2KD, 5 mice at 10 weeks; JAK2V617F, 5 mice at 16 weeks; double mutant, 5 mice at 13 weeks)

2014-10-16 | E-GEOD-62302 | biostudies-arrayexpress

Gene expression data from lineage negative c-kit positive sca-1 positive hematopoietic stem cells (LSK, Lin-Sca-1+c-kit+) isolated from Jak2VF/+ vector and Jak2VF/+ Hmga2 mice

Project description:The JAK2V617F mutation has been detected in ~50% cases of MF. Elevated expression of high mobility group AT hook 2 (HMGA2) also has been frequently observed in patients with MF. Interestingly, upregulation of HMGA2 expression has been found in association with the JAK2V617F mutation in significant cases of MF. However, the contribution of HMGA2 in the pathogenesis of MF remains elusive. To determine the effects of concurrent expression of HMGA2 and JAK2V617F mutation in hematopoiesis, we transduced bone marrow cells from Jak2V617F knock-in mice with lentivirus expressing Hmga2 and performed bone marrow transplantation. In order to assess the effects of Hmga2 overexpression on gene expression, we performed RNA sequencing analysis for the LSK from Jak2VF/+ vector and Jak2VF/+ Hmga2mice.

2017-08-01 | GSE99485 | GEO

Expression data from Lineage-c-Kit+Sca-1+ (LSK) and megakaryocyte/erythroid progenitor (MEP) cells isolated from WT, Ezh2?/?, JAK2V617F, and JAK2V617F/Ezh2?/? mice

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

H3K27me3 ChIP-sequencing on LSK (Lin-Sca-1+c-kit+) cells isolated from control, MxCre Jak2VF/+ and MxCre Jak2VF/+ EZH2-/- mice

Project description:Inactivating EZH2 mutations have been associated with myelofibrosis (MF). Moreover, EZH2 mutations co-exist with the JAK2V617F mutation in a significant cases of MF. To determine the effects of concomitant loss of EZH2 and JAK2V617F mutation in hematopoiesis, we generated Ezh2-deficient Jak2V617F-expressing mice. To identify the Ezh2 target genes that are regulated by H3K27me3 in MF, we performed H3K27me3 ChIP-sequencing in sorted LSK cells from control, MxCre;Jak2VF/+ and MxCre;Jak2VF/+ EZH2-/- mice.

2016-04-19 | GSE79319 | GEO

Expression data from Lineage-c-Kit+Sca-1+ (LSK) and megakaryocyte/erythroid progenitor (MEP) cells isolated from WT, Ezh2Δ/Δ, JAK2V617F, and JAK2V617F/Ezh2Δ/Δ mice

2015-06-04 | GSE69498 | GEO

Expression data from Lineage-c-Kit+Sca-1+ (LSK) and megakaryocyte/erythroid progenitor (MEP) cells isolated from JAK2V617F/Ezh2?/? mice post JQ1 treatment

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

Expression data from Lineage-c-Kit+Sca-1+ (LSK) and megakaryocyte/erythroid progenitor (MEP) cells isolated from JAK2V617F/Ezh2Δ/Δ mice post JQ1 treatment

2015-06-04 | GSE69499 | GEO

Expression data from Sf3b1 heterozygous Lineage-c-Kit+Sca-1+ (LSK) bone marrow cells

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.

2013-09-20 | GSE51038 | GEO

Gene expression profiling to study the transcriptional consequences of Jak2V617F expression and/or Tet2 loss in murine hematopoietic stem cells

Project description:To interrogate the molecular pathways disrupted by Jak2V617F expression and/or Tet2 loss, Lin-negative, Sca-1-positive, c-kit-positive (LSK) hematopoietic progenitor cells were isolated from bone marrow of wild-type, Jak2V617F, Tet2-null or Jak2V617F/Tet2-null animals (n= 2-4 mice per group) and subjected to gene expression profiling.

2014-10-31 | E-MTAB-2986 | biostudies-arrayexpress

Expression data from diseased Ezh2 KO Lineage-c-Kit+Sca-1+ (LSK) bone marrow cells

Project description:Recent studies have shown that epigenetic regulator are mutated in myelodysplastic syndrome (MDS) patients. Ezh2 is frequently mutated in hematopoietic malignant patients, however, the pathophysiological role of Ezh2 mutations has not been elucidated yet. In this study, we examined the function of Ezh2 in murine hematopoietic disease. Ezh2 deleted mice with myeloid malignancies including MDS, Myelodysplasia/myeloneoplasm(MDS/MPN), Myelodysplasia/myeloneoplasm_thrombocytosis(MDS/MPN_TC)

2015-03-14 | GSE66897 | GEO

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