Robb L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Oncogene. 2007 Oct 15;26(47):6715-23. doi: 10.1038/sj.onc.1210756.
Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.
集落刺激因子和其他细胞因子通过其同源受体发出信号，以调节造血作用。在许多发育系统中，诱导信号决定细胞命运，与此类似，有人推测细胞因子通过其同源受体发出信号，可能在造血过程的谱系定向中发挥指导作用。与这种指导假说相对的是随机或许可假说。后者提出，确定特定造血谱系是一个独立于外在信号发生的事件。它预测细胞因子的作用是提供非特异性的存活和增殖信号。在本综述中，我们探讨细胞因子受体信号在造血过程中的作用，并考量这两种假说的证据。我们回顾了在体外或体内对受体基因表达进行基因操作的实验数据。在多能细胞中安装细胞因子受体的实验表明，在某些情况下，用同源配体刺激可导致谱系输出的改变。基因操作小鼠品系的创建表明，细胞因子受体是单个谱系扩增和存活所必需的，但未揭示其在谱系定向中的作用。我们得出结论，造血分化主要涉及随机事件，但细胞因子受体也具有一定的指导作用。
