Antagonistic Effect of C/EBPα and Pax5 in Myeloid or Lymphoid Lineage Choice in Common Lymphoid Progenitors.

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. The transcription factor C/EBPa is promptly upregulated in CLPs upon ectopic IL-2 stimulation. We show that enforced C/EBPa 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 following ectopic IL-2 stimulation. Expression of Pax5, a B lymphoid affiliated transcription factor, is completely suppressed by enforced C/EBPa 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/EBPa is a proximal target of cytokine induced lineage conversion in lymphoid progenitors. Furthermore, complete loss of Pax5 expression triggered by upregulation of C/EBPa is a critical event for lineage conversion from lymphoid to myeloid lineage in CLPs and proB cells.