Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

Chia Lin Hsu, Angela G. King-Fleischman, Anne Y. Lai, Yukie Matsumoto, Irving L. Weissman*, Motonari Kondo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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-α (C/EBPα) is promptly up-regulated in CLPs upon ectopic IL-2 stimulation. Enforced C/EBPα 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/EBPα 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/EBPα is a proximal target of cytokine-induced lineage conversion in lymphoid progenitors. Furthermore, complete loss of Pax5 expression triggered by up-regulation of C/EBPα is a critical event for lineage conversion from lymphoid to myeloid lineage in CLPs and proB cells.

Original languageEnglish
Pages (from-to)672-677
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number3
DOIs
StatePublished - 17 Jan 2006

Keywords

  • Commitment
  • Cytokine receptor signaling
  • Hematopoiesis
  • Lineage instruction
  • Transcription factor

Fingerprint

Dive into the research topics of 'Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors'. Together they form a unique fingerprint.

Cite this