C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells.
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.
['Cirovic|Branko|B|', 'Schönheit|Jörg|J|', 'Kowenz-Leutz|Elisabeth|E|', 'Ivanovska|Jelena|J|', 'Klement|Christine|C|', 'Pronina|Nina|N|', 'Bégay|Valérie|V|', 'Leutz|Achim|A|']
D000818:Animals D001402:B-Lymphocytes D022762:CCAAT-Enhancer-Binding Proteins D002454:Cell Differentiation D019070:Cell Lineage D049109:Cell Proliferation D054338:Cell Transdifferentiation D018628:Gene Dosage D055014:Granulocyte-Macrophage Progenitor Cells D006410:Hematopoiesis D006412:Hematopoietic Stem Cells D006801:Humans D051379:Mice D005810:Multigene Family D010641:Phenotype
progenitor lineage switch differentiation hematopoiesis leukemia stem cell