Myeloid lineage switch of Pax5 mutant but not wild-type B cell progenitors by C/EBPα 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 eryth...
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Veröffentlicht in: | The EMBO journal 2003-08, Vol.22 (15), p.3887-3897 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0261-4189 1460-2075 |
DOI: | 10.1093/emboj/cdg380 |