title: C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells.
abstract: The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBPα, β, δ, and ε) were compared in v-Abl-immortalized primary B cells. Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBPα and β activation. High transgene expression of C/EBPβ or C/EBPε, but not of C/EBPα or C/EBPδ, also induced the formation of granulocytes. Granulocytes and macrophages emerged in a mutually exclusive manner. C/EBPβ-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. The GMP-like progenitors remained self-renewing and cytokine-independent, and continuously produced macrophages and granulocytes. In addition to their suitability to study myelomonocytic lineage bifurcation, lineage-switched GMP-like progenitors could reflect the features of the lympho-myeloid lineage switch observed in leukemic progression.
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany; Humboldt-University of Berlin, Institute of Biology, 10115 Berlin, Germany.
authors.forename: Branko
authors.initials: B
authors.lastname: Cirovic
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schönheit
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kowenz-Leutz
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Ivanovska
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klement
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Pronina
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bégay
authors.affiliation: Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany; Humboldt-University of Berlin, Institute of Biology, 10115 Berlin, Germany. Electronic address: aleutz@mdc-berlin.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Leutz
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000235:genetics*; D018628:Gene Dosage; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D005810:Multigene Family; D010641:Phenotype
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins
keywords: differentiation; hematopoiesis; leukemia; lineage switch; progenitor; stem cell