C/EBP-induced transdifferentiation reveals granulocyte-macrophage precursor-like plasticity of B cells


  • B. Cirovic
  • J. Schönheit
  • E. Kowenz-Leutz
  • J. Ivanovska
  • C. Klement
  • N. Pronina
  • V. Bégay
  • A. Leutz


  • Stem Cell Reports


  • Stem Cell Rep 14 (8): 346-359


  • The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBP{alpha}, {beta}, {delta}, and {epsilon}) 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/EBP{alpha} and {beta} activation. High transgene expression of C/EBP{beta} or C/EBP{epsilon}, but not of C/EBP{alpha} or C/EBP{delta}, also induced the formation of granulocytes. Granulocytes and macrophages emerged in a mutually exclusive manner. C/EBP{beta}-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.