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Next Generation Sequencing of megakaryocyte-erythrocyte progenitor cells (MEPs) with or without mutations in JAK2 and Ezh2

ABSTRACT: Comparison of mRNA expression profiles of MEPs with or without mutations in JAK2 and Ezh2 by RNA sequencing. MEPs mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of MEP with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. Our results revealed that mRNA expression profile of MEP with different genotype showed specific gene expression patterns, which allows to do biological comprehensive and quantitative analysis for hematopoiesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE82072 | GEO | 2016/06/24

SECONDARY ACCESSION(S): PRJNA323931

REPOSITORIES: GEO

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Next Generation Sequencing of megakaryocyte-erythrocyte progenitor cells (MEPs) with or without mutations in JAK2 and Ezh2

Project description:Comparison of mRNA expression profiles of MEPs with or without mutations in JAK2 and Ezh2 by RNA sequencing. MEPs mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of MEP with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. Our results revealed that mRNA expression profile of MEP with different genotype showed specific gene expression patterns, which allows to do biological comprehensive and quantitative analysis for hematopoiesis. MEPs mRNA profiles six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) were generated by deep sequencing.

2016-06-24 | E-GEOD-82072 | biostudies-arrayexpress

Next Generation Sequencing of long-term hematopoietic cells (LT-HSCs) with or without mutations in JAK2 and Ezh2

Project description:Comparison of mRNA expression profiles of LT-HSCs with or without mutations in JAK2 and Ezh2 by RNA sequencing. LT-HSC mRNA was extracted from six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) 10 weeks after tamoxifen injection. Our study represents the first detailed analysis of mRNA expression profile of LT-HSC with or without mutations in JAK2 and Ezh2 , with biologic replicates, generated by RNA-seq technology. Our results revealed that mRNA expression profile of LT-HSC with different genotype showed specific gene expression patterns, which allows to do biological comprehensive and quantitative analysis for hematopoiesis. LT-HSCs mRNA profiles six different transgenic mice (SclCre, SclCre;Ezh2+/-, SclCre;Ezh2-/-, SclCre; JAK2V617F, SclCre; JAK2V617F;Ezh2+/-, SclCre; JAK2V617F;Ezh2-/-) were generated by deep sequencing.

2016-06-24 | E-GEOD-82073 | biostudies-arrayexpress

Next Generation Sequencing of long-term hematopoietic cells (LT-HSCs) with or without mutations in JAK2 and Ezh2

2016-06-24 | GSE82073 | 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 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

Expression data from Ezh2-null erythrocyte/megakaryocyte progenitor (MEP)

Project description:The polycomb group (PcG) proteins function in gene silencing through histone modifications. They form chromatin-associated multiprotein complexes, termed polycomb repressive complex (PRC) 1 and PRC2. These two complexes work in a coordinated manner in the maintenance of cellular memories through transcriptional repression of target genes. EZH2 is a catalytic component of PRC2 and trimethylates histone H3 at lysine 27 to transcriptionally repress the target genes. PcG proteins have been characterized as general regulators of stem cells, but recent works also unveiled their critical roles in cancer. Wild type and Ezh2 null MEP from fetal liver and adult bone marrow

2011-12-27 | E-GEOD-32929 | biostudies-arrayexpress

Splicing factor Ybx1 maintains persistent Jak2-mutated neoplasms via Mknk1-ERK-signaling

Project description:Janus kinases (Jak) mediate cytokine, hormone and growth factor responses in hematopoietic cells. Jak2 is one of the most frequently mutated genes in the aging hematopoietic system and in hematopoietic cancers. Mutations in Jak constitutively activate downstream signaling and are drivers of myeloproliferative neoplasms (MPN). In clinical use, Jak-inhibitors have incomplete effects on overall disease burden of Jak2 mutated clones, prompting us to investigate the mechanism underlying disease persistence. By in-depth phospho-proteome profiling we here identify proteins involved in mRNA processing as targets of mutant Jak2. Inactivation of the post-translationally modified Jak2-target Ybx1 sensitizes Jak-inhibitor persistent cells to apoptosis and results in RNA mis-splicing, retained intron enrichment and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signaling. In combination with pharmacological Jak-inhibition it induces apoptosis in Jak2-dependent murine and primary human cells, leading to in vivo regression of the malignant clones and inducing remission. This identifies and validates a novel cell-intrinsic mechanism how differential protein phosphorylation results in splicing-dependent alterations of Jak2-ERK-signaling and the maintenance of Jak2V617F malignant clones. Therapeutic targeting of Ybx1 dependent ERK-signaling in combination with Jak2-inhibition may eradicate Jak2-mutated cells.

2020-08-20 | PXD006921 | Pride

megamiR, microRNA expression profiles during megakaryocyte-erythrocyte progenitor (MEP) differentiation

Project description:This collection contains microRNA expression profiling data for samples purified from umbilical cord blood, belonging to one of the followiing populations: MEP, MEGA1, MEGA2, ERY1, ERY2, ERY3. MEP: megakaryocyte-erythrocyte precursors (defined by CD34+ CD38+ IL-3Ra- CD45RA- ); MEGA1: megakaryocyte population 1 (defined by CD34+ CD61+ CD41+ CD45- ); MEGA2: megakaryocyte population 2 (defined by CD34- CD61+ CD41+ CD45- ); ERY1: erythrocyte population 1 (defined by CD34+ CD71+ GlyA- ); ERY2: erythrocyte population 2 (defined by CD34- CD71+ GlyA- ); ERY3: erythrocyte population 3 (defined by CD34- CD71+ GlyA+ ). Keywords: microRNA, miRNA, MEP, megakaryocyte, erythrocyte, lineage specification

2008-06-10 | GSE10593 | GEO

RNA sequencing of LSK cells from mice with JAK2 mutation and HMGA2 expression

Project description:Either loss of EZH2 or redcuction of let-7 induces expression of HMGA2 and provokes severe myelofibrosis in mice carrying JAK2V617F. Therefore we compared gene expression profiles of LSK cells among WT mice, Hmga2-Tg mice, JAK2V617F-Tg mice, JAK2V617F/Hmga2 double-Tg mice, and JAK2V617F-Tg/EZH2 conditional KO mice.

2017-06-01 | GSE87464 | GEO

Myeloproliferative neoplasms show different signature in megakaryocyte-erythroid progenitors among different subtypes

Project description:In this study, we explored the transcriptome of megakaryocyte-erythroid progenitors (MEPs) in JAK2 V617F+ PV and ET and found distinctive gene expression patterns within MPN subtypes. The differentially expressed genes (DEGs) indicated that cellular processes and signaling pathways in MEPs from healthy donors (HDs, or NCs) are differentially modulated in PV and ET patients.

2023-04-12 | GSE168368 | GEO

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