Duff Campbell, Smith-Miles Kate, Lopes Leo, Tian Tianhai
School of Mathematical Sciences, Monash University, Melbourne, VIC, 3800, Australia.
J Math Biol. 2012 Feb;64(3):449-68. doi: 10.1007/s00285-011-0419-3. Epub 2011 Apr 2.
The transcription factors PU.1 and GATA-1 are known to be important in the development of blood progenitor cells. Specifically they are thought to regulate the differentiation of progenitor cells into the granulocyte/macrophage lineage and the erythrocyte/megakaryocite lineage. While several mathematical models have been proposed to investigate the interaction between the transcription factors in recent years, there is still debate about the nature of the progenitor state in the dynamical system, and whether the existing models adequately capture new knowledge about the interactions gleaned from experimental data. Further, the models utilise different formalisms to represent the genetic regulation, and it appears that the resulting dynamical system depends upon which formalism is adopted. In this paper we analyse the four existing models, and propose an alternative model which is shown to demonstrate a rich variety of dynamical systems behaviours found across the existing models, including both bistability and tristability required for modelling the undifferentiated progenitors.
已知转录因子PU.1和GATA-1在血液祖细胞的发育过程中起着重要作用。具体而言，它们被认为可调节祖细胞向粒细胞/巨噬细胞谱系以及红细胞/巨核细胞谱系的分化。尽管近年来已提出了几个数学模型来研究转录因子之间的相互作用，但对于动态系统中祖细胞状态的本质，以及现有模型是否充分捕捉了从实验数据中获得的关于相互作用的新知识，仍存在争议。此外，这些模型使用不同的形式来表示基因调控，并且由此产生的动态系统似乎取决于所采用的形式。在本文中，我们分析了四个现有模型，并提出了一个替代模型，该模型被证明展示了现有模型中发现的丰富多样的动态系统行为，包括模拟未分化祖细胞所需的双稳态和三稳态。
