Abstract
The development of red blood cells from hematopoietic progenitors requires the interplay of specific extracellular factors and transcriptional regulators. Here we have identified an erythroid progenitor that is critically dependent on bFGF and requires expression of AMV v-Myb for sustained proliferation in vitro, indicating that bFGF and Myb proteins cooperate in these cells. In the presence of bFGF such v-Myb cells are completely blocked in their ability to differentiate and exhibit an exceptionally high proliferative potential and long lifespan in vitro. Interestingly, in the absence of bFGF cells effectively differentiate into mature erythrocytes, irrespective of constitutive and elevated levels of v-Myb. We also demonstrate that these cells express high levels of FGF receptor type 1 (FGFR1) and that phospholipase Cγ (PLCγ) is one of the important molecules in FGF receptor signaling. Our studies suggest that bFGF, in cooperation with Myb proteins, represents an important factor for determining erythroid lineage choice. These findings unravel a so far unidentified link between extracellular signaling and Myb in hematopoietic cells.
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Acknowledgements
We thank C Corbel, DL Ewert, J Kaufmann and O Vainio for monoclonal antibodies, J Lipsick and E Pasquale for recombinant plasmid DNA, H Beug and G Christofori for critical reading of the manuscript and I Gallagher for typing the manuscript. This work was funded by grants from the Grant Agency of the Czech Republic 301/98/K042 and 204/00/0554, by the grant A5052805 from the Grant Agency of the Academy of Sciences of the Czech Republic to M Dvořák, a grant of the Fonds der Chemischen Industrie to M Zenke, and by the grant from Howard Hughes Medical Institute (HHMI, No. 75195-540401) to M Dvořák and M Zenke. M Dvořák was an International Research Scholar of the Howard Hughes Medical Institute.
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Bartůněk, P., Pajer, P., Karafiát, V. et al. bFGF signaling and v-Myb cooperate in sustained growth of primitive erythroid progenitors. Oncogene 21, 400–410 (2002). https://doi.org/10.1038/sj.onc.1205103
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DOI: https://doi.org/10.1038/sj.onc.1205103