Centre d'Immunologie de Marseille-Luminy (CIML), Université Aix-Marseille, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.
Semin Immunol. 2011 Oct;23(5):326-34. doi: 10.1016/j.smim.2011.08.011. Epub 2011 Sep 19.
In the predominant model of hematopoietic stem cell differentiation lineage commitment is thought to be initiated by stochastic variation in the balance of lineage determining transcription factors, whereas cytokines have been seen in a purely permissive role of stimulating selective survival and proliferation of the down stream progeny. Recent observations, however, indicate that cytokines can also directly instruct cell fate change in uncommitted stem and progenitor cells by activating lineage determining transcription factors. We review the historic and recent evidence for instructive cytokine signaling and propose a model that integrates cytokine signaling and transcription factor activity in the initial decision making process, where the sensitivity to external instructive signals can be modulated by internal threshold setters. In contrast to a rigid stochastic explanation of lineage commitment this view allows for receptiveness of the hematopoietic stem cell to its environment and exposes lineage commitment as dependent on both instructive signals and cell intrinsically controlled sensitivity to external cues.
在造血干细胞分化谱系定向的主要模型中，人们认为谱系决定转录因子的平衡随机变化启动了细胞定向，而细胞因子则被视为仅具有刺激下游祖细胞选择性存活和增殖的许可作用。然而，最近的观察结果表明，细胞因子也可以通过激活谱系决定转录因子，直接在未定向的干细胞和祖细胞中指导细胞命运的改变。我们回顾了有指导意义的细胞因子信号的历史和最新证据，并提出了一个模型，该模型将细胞因子信号和转录因子活性整合到初始决策过程中，其中对外在有指导意义的信号的敏感性可以通过内部门控器来调节。与谱系定向的严格随机解释相反，这种观点允许造血干细胞对其环境的敏感性，并揭示了谱系定向取决于有指导意义的信号和细胞内在控制对外部线索的敏感性。
