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Haematologica. 2019 May 23. pii: haematol.2019.217596. doi: 10.3324/haematol.2019.217596. [Epub ahead of print]

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

Author information

1
Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine.
2
Université de Paris 7/INSERM/CNRS UMR 944/7212.
3
Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University.
4
Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine; zj10802@rjh.com.cn.

Abstract

Proper cell fate choice of neutrophil-macrophage progenitor is essential for adequate myeloid sub-populations during embryonic development and in adulthood. The network governing neutrophil-macrophage progenitor cell fate is composed of several key determinants such as myeloid master regulators CCAAT enhancer binding protein alpha (C/EBPα) 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 progenitor 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 choice which favors macrophages at the expense of neutrophils during the zebrafish definitive myelopoiesis stage in deficient embryos. Mechanistic studies indicate that Interferon regulatory factor 2 binding protein 2b acts as a downstream target of CCAAT enhancer binding protein alpha, to repress spleen focus forming virus proviral integration oncogene expression, and that SUMOylation confers the repressive function of Interferon regulatory factor 2 binding protein 2b. Thus, Interferon regulatory factor 2 binding protein 2b is a novel determinant in the cell fate choice of neutrophil-macrophage progenitor.

KEYWORDS:

Granulocytes, Monocytes, Macrophages; Hematopoiesis; Irf2bp2b; NMPs cell fate choice; SUMOylation

PMID:
31123027
DOI:
10.3324/haematol.2019.217596
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