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| Subject Categories: Chromatin & Transcription | Immunology |
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| The EMBO Journal
(2003) 22, 3887–3897, doi:10.1093/emboj/cdg380 |
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Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by C/EBP and GATA factors |
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| Barry Heavey2, 3, Christoforos Charalambous1, 3, Cesar Cobaleda1 and Meinrad Busslinger1 |
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1 Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria 2 Present address: Institute for Stem Cell Research, Kings Buildings, West Mains Road, Edinburgh EH9 3JQ, UK 3 B.Heavey and C.Charalambous contributed equally to this work To whom correspondence should be addressed Meinrad Busslinger, busslinger@nt.imp.univie.ac.at Received 19 August 2002; Revised 5 June 2003; Accepted 10 June 2003. |
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| Abstract |
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| 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/EBP, 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/EBP 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. |
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| Keywords: C, EBP, GATA factors, Pax5 mutantpro-B cells, myeloid lineage switch |
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