Estrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced myeloproliferative neoplasm in vivo, and sensitized MLL-AF9+ leukemias to chemotherapy. Tamoxifen showed selective effects on mutant cells compared to normal ones, and had only a minor impact on steady-state hematopoiesis in disease-free animals. These results uncover specific regulation of hematopoietic progenitors by estrogens and potential anti-leukemic properties of SERM Overall design: LT-HSCs, ST-HSCs and MPPs sorted from the bone marrow of mice treated with tamoxifen or vehicle (3 biological replicates per group)
Estrogen signaling selectively induces apoptosis of hematopoietic progenitors and myeloid neoplasms without harming steady-state hematopoiesis.
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View SamplesComparison 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. Overall design: 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.
Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis.
Sex, Subject
View SamplesComparison 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. Overall design: 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.
Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis.
Sex, Subject
View SamplesTranscriptomal comparison between group 2 innate lymphoid cells (ILC2s) in the murine small intestine (SI-ILC2s) and those in white adipose tissue (WAT-ILC2s). Overall design: mRNA profiles of group 2 innate lymphoid cells (ILC2s) sort-purified from small intestinal lamina propria and mesenteric white adipose tissue of 9-week-old wild type (WT) mice were generated by sequencing, in duplicate, using Illumina HiSeq1500.
Innate Lymphoid Cells in the Induction of Obesity.
Age, Specimen part, Subject
View SamplesExpression profile of embryonic retinas expressing exogenous c-hairy1, Delta-1, or Wnt2b. These genes inhibits neuronal differentiation, and the results provide insight into the mechanism that keeps retinal progenitor cells undifferentiated.
Hairy1 acts as a node downstream of Wnt signaling to maintain retinal stem cell-like progenitor cells in the chick ciliary marginal zone.
Specimen part
View SamplesIn hemochorial placentation, trophoblast stem cells differentiate into multiple lineages to aquire specific functions, such as invasive and endocrine phenotype. FOSL1 has been identified as a key regulator for trophoblast differentiation. We used microarray to detail mechanisms underlying FOSL1 signaling pathway in trophoblast differentiation.
Dynamic Regulation of AP-1 Transcriptional Complexes Directs Trophoblast Differentiation.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection.
Sex, Specimen part
View SamplesBmdm cells were differentiated for 10 days and harvested and culture in six well plate followed by cytokine stimulation
Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection.
Sex, Specimen part
View SamplesBmdm cells were differentiated for 10 days and harvested and culture in six well plate followed by transfection with Batf2 ShRNA.
Batf2/Irf1 induces inflammatory responses in classically activated macrophages, lipopolysaccharides, and mycobacterial infection.
Sex, Specimen part
View SamplesThe liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secreted proteins, termed hepatokines.
A liver-derived secretory protein, selenoprotein P, causes insulin resistance.
Sex, Specimen part, Disease
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