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Publication : Antagonistic effect of CCAAT enhancer-binding protein-alpha and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors.

First Author  Hsu CL Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  3 Pages  672-7
PubMed ID  16407117 Mgi Jnum  J:105665
Mgi Id  MGI:3616285 Doi  10.1073/pnas.0510304103
Citation  Hsu CL, et al. (2006) Antagonistic effect of CCAAT enhancer-binding protein-alpha and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors. Proc Natl Acad Sci U S A 103(3):672-7
abstractText  Lymphoid lineage-committed progenitors, such as common lymphoid progenitors (CLPs), maintain a latent myeloid differentiation potential, which can be initiated by stimulation through exogenously expressed cytokine receptors, including IL-2 receptors. Here we show that the transcription factor CCAAT enhancer-binding protein-alpha (C/EBPalpha) is promptly up-regulated in CLPs upon ectopic IL-2 stimulation. Enforced C/EBPalpha expression is sufficient to initiate myeloid differentiation from CLPs, as well as from proT and proB cells, even though proB cells do not give rise to myeloid cells after ectopic IL-2 stimulation. Expression of Pax5, a B lymphoid-affiliated transcription factor, is completely suppressed by enforced C/EBPalpha but not by ectopic IL-2 stimulation in proB cells. Introduction of Pax5 blocks ectopic IL-2 receptor-mediated myeloid lineage conversion in CLPs. These data suggest that C/EBPalpha is a proximal target of cytokine-induced lineage conversion in lymphoid progenitors. Furthermore, complete loss of Pax5 expression triggered by up-regulation of C/EBPalpha is a critical event for lineage conversion from lymphoid to myeloid lineage in CLPs and proB cells.
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