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Gene epxression profiling in murine Flt3+ granulocyte progenitors (Flt3+ GPs) and Flt3- granulocyte progenitors (Flt3- GPs)

ABSTRACT: To understand the mechanism by which IRF8 promotes basophil differentiation Murine bone marrow Flt3+ GPs and Flt3- GPs were isolated by cell sorting from wild-type or Irf8 deficient mice. Two independent experiments were performed.

ORGANISM(S): Mus musculus

SUBMITTER: Tomohiko Tamura

PROVIDER: E-GEOD-54887 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene epxression profiling in murine Flt3+ granulocyte progenitors (Flt3+ GPs) and Flt3- granulocyte progenitors (Flt3- GPs)

Project description:To understand the mechanism by which IRF8 promotes basophil differentiation

2014-11-17 | GSE54887 | GEO

Gene expression profiling in murine monocyte-dendritic cell progenitors (MDPs), common monocyte progenitors (cMoPs) and 32Dcl.3 cells transduced with C/EBPalpha and/or IRF8

Project description:To understand the mechanism by which IRF8 inhibits neutrophil differentiation Murine bone marrow MDPs and cMoPs were isolated by cell sorting from wild-type or Irf8 deficient mice. 32Dcl.3 cells were transduced with retroviruses carrying murine C/EBPalpha cDNA and/or murine Irf8 cDNA. Two independent experiments were performed.

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Gene epxression profiling in murine bone marrow Lin- cells transduced with BCR-ABL and/or IRF8 followed by Flt3L culture for 5 days

Project description:To understand the effect of BCR-ABL and IRF8 on gene expression pattern during in vitro dendritic cell differentiation, microarry analysis was performed. Murine bone marrow Lin- cells were transduced with retroviruses carrying human BCR-ABL cDNA and/or mouse Irf8 cDNA, and then cultured with Flt3L for 5 days. Two independent experiments were performed.

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The Granulocyte Progenitor Stage is a Key Target of IRF8-Mediated Regulation of Myeloid-Derived Suppressor Cell Production

Project description:Alterations in myelopoiesis are common across various tumor types, resulting in immature populations termed myeloid-derived suppressor cells (MDSCs). MDSC burden correlates with poorer clinical outcomes, credited to their ability to suppress antitumor immunity. MDSCs consist of two major subsets, monocytic and polymorphonuclear (PMN). Intriguingly, the latter subset predominates in many patients and tumor models, though the mechanisms favoring PMN-MDSC responses remain poorly understood. Ordinarily, lineage-restricted transcription factors regulate myelopoiesis that collectively dictate cell fate. One integral player is interferon regulatory factor-8 (IRF8), which promotes monocyte/dendritic cell differentiation while limiting granulocyte development. We recently showed that IRF8 inversely controls MDSC burden in tumor models, particularly the PMN-MDSC subset. However, where IRF8 acts in the pathway of myeloid differentiation to influence PMN-MDSC production has remained unknown. Here, we showed that: 1) tumor growth was strongly associated with a selective expansion of newly defined IRF8lo granulocytic progenitors (GPs); 2) tumor-derived GPs had an increased ability to form PMN-MDSCs; 3) tumor-derived GPs shared gene expression patterns with IRF8-/- GPs, suggesting that IRF8 loss underlies GP expansion; and 4) enforced IRF8 overexpression in vivo selectively constrained tumor-induced GP expansion. These findings support the hypothesis that PMN-MDSCs result from selective expansion of IRF8lo GPs, and that strategies targeting IRF8 expression may limit their load to improve immunotherapy efficacy.

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The Granulocyte Progenitor Stage is a Key Target of IRF8-Mediated Regulation of Myeloid-Derived Suppressor Cell Production

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Gene expression analysis of WT and Flt3-ITD multipotent progenitors

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A combined gas phase separation strategy for ADP-ribosylated peptides

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Fetal and neonatal hematopoietic progenitors are functionally and transcriptionally resistant to Flt3-ITD mutations.

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