C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells

Stem Cell Reports

Elisabeth Kowenz-Leutz¹  Jelena Ivanovska¹  Nina Pronina¹  Branko Cirovic¹  Christine Klement¹  Valérie Bégay¹  Achim Leutz¹  Jörg Schönheit¹ 

[1] Department of Tumorigenesis and Cell Differentiation, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Straße10, 13125 Berlin, Germany;

关键词: hematopoiesis;    leukemia;    differentiation;    stem cell;    progenitor;    lineage switch;   

DOI  :  10.1016/j.stemcr.2016.12.015

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown