A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation.

A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation.
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G-CSF 受体信号传导在造血细胞功能调节中的作用,但在谱系定型或分化中没有作用。

DOI:
10.1016/s1074-7613(00)80090-4
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发表时间:
1999
期刊:
影响因子:
32.4
通讯作者:
Link,DC
Link,DC
中科院分区:
医学1区
文献类型:
--
作者:
Semerad,CL;Poursine-Laurent,J;Liu,F;Link,DC

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为了研究造血分化中细胞因子信号的特异性,我们产生了具有其G-CSF受体(G-CSFR)的靶向突变的小鼠,使得G-CSFR的胞质(信号传导)结构域被促红细胞生成素受体的胞质结构域取代。在纯合子突变小鼠中,这种嵌合受体的表达对谱系定型没有明显影响,并且能够支持形态成熟的中性粒细胞的产生。然而,突变的中性粒细胞显示趋化性降低,G-CSF刺激的中性粒细胞和造血祖细胞从骨髓到血液的动员明显受损。因此,G-CSFR产生特定造血细胞功能所需的独特信号,但不需要粒细胞分化或谱系定型。
To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, expression of this chimeric receptor had no apparent affect on lineage commitment and was able to support the production of morphologically mature neutrophils. However, mutant neutrophils displayed reduced chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoietic progenitors from the bone marrow to blood was markedly impaired. Thus, the G-CSFR is generating unique signals that are required for certain specialized hematopoietic cell functions but are not required for granulocytic differentiation or lineage commitment.
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