Interferon regulatory factor 2 binding protein 2b regulates neutrophil versus macrophage fate during zebrafish definitive myelopoiesis

Authors：Wang, Luxiang; Gao, Shuo; Wang, Haihong; Xue, Chang; Liu, Xiaohui; Yuan, Hao; Wang, Zixuan; Chen, Saijuan; Chen, Zhu; de The, Hugues; Zhang, Yiyue; Zhang, Wenqing^*; Zhu, Jun^*; Zhou, Jun^*

Source：Haematologica, 2020, 105(2): 325-337.

DOI：10.3324/haematol.2019.217596

• TRANSCRIPTIONAL REPRESSOR GFI-1
• ACUTE PROMYELOCYTIC LEUKEMIA
• C/EBP-ALPHA BINDS
• ZINC-FINGER
• PU.1
• IDENTIFICATION
• IRF2BP2-RARA
• EXPRESSION
• GENE
• INFLAMMATION

A proper choice of neutrophil-macrophage progenitor cell fate is essential for the generation of adequate myeloid subpopulations uring embryonic development and in adulthood. The network governing neutrophil-macrophage progenitor cell fate has several key determinants, such as myeloid master regulators CCAAT enhancer binding protein alpha (C/EBP alpha) and spleen focus forming virus proviral integration oncogene (PU.1). Nevertheless, more regulators remain to be identified and characterized. To ensure balanced commitment of neutrophil-macrophage progenitors toward each lineage, the interplay among these determinants is not only synergistic, but also antagonistic. Depletion of interferon regulatory factor 2 binding protein 2b (Irf2bp2b), a well-known negative transcription regulator, results in a bias in neutrophil-macrophage progenitor cell fate in favor of macrophages at the expense of neutrophils during the stage of definitive myelopoiesis in zebrafish embryos. Mechanistic studies indicate that Irf2bp2b acts as a downstream target of C/EBP alpha, repressing PU.1 expression, and that SUMOylation confers the repressive function of Irf2bp2b. Thus, Irf2bp2b is a novel determinant in the choice of fate of neutrophil-macrophage progenitor cells.

• Institution
  上海交通大学