Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by C/EBP and GATA factors

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Abstract
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/EBPα, 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/EBPα 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.