Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by C/EBPalpha and GATA factors.
The developmental potential of hematopoietic progenitors is restricted early on to either the erythromyeloid or lymphoid lineages. The broad developmental potential of Pax5(-/-) pro-B cells is in apparent conflict with such a strict separation, although these progenitors realize the myeloid and erythroid potential with lower efficiency compared to the lymphoid cell fates. Here we demonstrate that ectopic expression of the transcription factors C/EBPalpha, GATA1, GATA2 and GATA3 strongly promoted in vitro macrophage differentiation and myeloid colony formation of Pax5(-/-) pro-B cells. GATA2 and GATA3 expression also resulted in efficient engraftment and myeloid development of Pax5(-/-) pro-B cells in vivo. The myeloid transdifferentiation of Pax5(-/-) pro-B cells was accompanied by the rapid activation of myeloid genes and concomitant repression of B-lymphoid genes by C/EBPalpha and GATA factors. These data identify the Pax5(-/-) pro-B cells as lymphoid progenitors with a latent myeloid potential that can be efficiently activated by myeloid transcription factors. The same regulators were unable to induce a myeloid lineage switch in Pax5(+/+) pro-B cells, indicating that Pax5 dominates over myeloid transcription factors in B-lymphocytes.
Heavey
Barry
B
Research Institute of Molecular Pathology, Vienna Biocenter,Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Charalambous
Christoforos
C
Cobaleda
Cesar
C
Busslinger
Meinrad
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology*; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D051757:PAX5 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D014157:Transcription Factors