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Growth factor independence 1 (Gfi1) regulates cell-fate decision of the bipotential granulocytic-monocytic precursor defined by the expression of CD48 as a new marker

ABSTRACT: Using bone marrow cells of GFP:Gfi1 knock in mice, we separated Gfi1-high and Gfi1-low expressing cells in the classical CD11b+, GR1-low monocytic cell fraction. We sorted CD11b+, GR1-low GFP:Gfi1-high and low cells as well as CD11b+, GR1-high granulocytes and CD11b-high, GR1-intermediate cells from Gfi1-knock-out mice for further analysis. We used Affymetrix Mouse Genome 430A 2.0 arrays (GPL8321) The study should determine how Gfi1 regulates the cell fate of monocytes/granulocytes in mice

ORGANISM(S): Mus musculus

SUBMITTER: Lothar Vassen

PROVIDER: E-GEOD-35970 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Growth factor independence 1 (Gfi1) regulates cell-fate decision of the bipotential granulocytic-monocytic precursor defined by the expression of CD48 as a new marker

Project description:Using bone marrow cells of GFP:Gfi1 knock in mice, we separated Gfi1-high and Gfi1-low expressing cells in the classical CD11b+, GR1-low monocytic cell fraction. We sorted CD11b+, GR1-low GFP:Gfi1-high and low cells as well as CD11b+, GR1-high granulocytes and CD11b-high, GR1-intermediate cells from Gfi1-knock-out mice for further analysis. We used Affymetrix Mouse Genome 430A 2.0 arrays (GPL8321)

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Growth factor independence 1 (Gfi1) as a new target for leukemia therapy

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Growth factor independence 1 (Gfi1) regulates cell-fate decision of a bipotential granulocytic-monocytic precursor defined by expression of Gfi1 and CD48.

Project description:The transcriptional repressor Gfi1 regulates the expression of genes important for survival, proliferation and differentiation of hematopoietic cells. Gfi1 deficient mice are severely neutropenic and accumulate ill-defined CD11b(+)GR1(int) myeloid cells. Here we show that Gfi1 expression levels determine mono- or granulocytic lineage choice in precursor cells. In addition, we identify CD48 as a cell surface marker which enables a better definition of monocytes and granulocytes in mouse bone marrow. Using the CD48/Gr1/Gfi1 marker combination we can show that the CD11b(+)GR1(int) cells accumulating in Gfi1 deficient mice are monocytes and not granulocyte precursors. Expression of CD48, Gr1 and Gfi1 define different bone marrow subpopulations that are either committed to the granulocytic lineage, or bipotential precursors of granulocytes or monocytes. Finally, a comparison of genes differentially expressed between murine Gfi1 high granulocytic precursors and mature granulocytes with gene expression changes from human myeloblasts versus neutrophils show a strong resemblance of human and mouse differentiation pathways. This underlines the value of the markers CD48 and Gfi1 identified here to study human and murine granulo-monocytic differentiation.

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