PU.1 and the granulocyte- and macrophage colony-stimulating factor receptors play distinct roles in late-stage myeloid cell differentiation
PU.1 and the granulocyte- and macrophage colony-stimulating factor receptors play distinct roles in late-stage myeloid cell differentiation
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DOI：
10.1182/blood.v94.7.2310.419k34_2310_2318
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发表时间：
1999-10-01
期刊：
影响因子：
20.3
通讯作者：
Torbett, BE
中科院分区：
文献类型：
--
作者：
Anderson, KL;Smith, KA;Torbett, BE
PU.1是造血细胞特异性ETS家族转录因子。 PU.1的基因破坏导致造血祖细胞细胞中细胞自主缺陷，表现为异常的髓样和B淋巴发育。在髓样谱系中，没有成熟的巨噬细胞发展，并且形成的中性粒细胞异常且不完全成熟。 PU.1 NULL（缺乏）造血细胞的文献异常之一是未能表达粒细胞刺激因子（G-CSF）（G-CSF），粒细胞 - 巨噬细胞（GM）-CSF和M-CSF的受体，无法阐明该受体。髓样生长因子受体在髓样细胞分化中的作用，并将其作用与PU.1的作用区分开使用逆转录病毒载体恢复了PU.1缺陷细胞中G-和Wi-CSF受体的表达。我们在这些细胞中也同样表达了pu.1。而生长因子受体的表达仅允许PU.1缺陷型细胞系在相关生长因子中生存和生长，而PU.1的表达使F4/80（+），MAC-1（+）/CD11B的发展能够发展（+）巨噬细胞，GP91（PHOX）的表达和超氧化物的产生，以及用于中性粒细胞胶原酶和明胶酶的继发颗粒基因的表达，这些研究增强了PU.1的可用性对于正常的髓样发育至关重要，并阐明了发展中性粒细胞和巨噬细胞的某些分子事件，这些事件严重依赖于PU.1。 （c）1999年美国血液学学会。
PU.1 is a hematopoietic cell-specific ets family transcription factor. Gene disruption of PU.1 results in a cell autonomous defect in hematopoietic progenitor cells that manifests as abnormal myeloid and B-lymphoid development. Of the myeloid lineages, no mature macrophages develop, and the neutrophils that develop are aberrantly and incompletely matured. One of the documented abnormalities of PU.1 null (deficient) hematopoietic cells is a failure to express receptors for granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and M-CSF, To elucidate the roles of the myeloid growth factor receptors in myeloid cell differentiation, and to distinguish their role from that of PU.1, we have restored expression of the G- and WI-CSF receptors in PU.1-deficient cells using retroviral vectors. We have similarly expressed PU.1 in these cells. Whereas expression of growth factor receptors merely allows a PU.1-deficient cell line to survive and grow in the relevant growth factor, expression of PU.1 enables the development of F4/80(+), Mac-1(+)/CD11b(+) macrophages, expression of gp91(phox) and generation of superoxide, and expression of secondary granule genes for neutrophil collagenase and gelatinase, These studies reinforce the idea that availability of PU.1 is crucial for normal myeloid development and clarify some of the molecular events in developing neutrophils and macrophages that are critically dependent on PU.1. (C) 1999 by The American Society of Hematology.