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Myeloid lineage switch of Pax5 mutant but not wild‐type B cell progenitors by C/EBPα and GATA factors
Author(s) -
Heavey Barry,
Charalambous Christoforos,
Cobaleda Cesar,
Busslinger Meinrad
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg380
Subject(s) - biology , myeloid , haematopoiesis , progenitor cell , gata2 , microbiology and biotechnology , b cell , irf8 , cellular differentiation , ectopic expression , transcription factor , immunology , stem cell , genetics , cell culture , gene , antibody
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.