Genetic analysis of differentiation of T-helper lymphocytes
Genetic analysis of differentiation of T-helper lymphocytes
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DOI：
10.4238/2013.april.2.13
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发表时间：
2013-01-01
影响因子：
0.4
通讯作者：
Gao, M.
中科院分区：
文献类型：
--
作者：
Wang, Q.;Li, M.;Gao, M.
在人体免疫系统中，t辅助细胞能够分化为两个淋巴细胞亚群：Th1和Th2。细胞内分化信号通路通过分泌不同类型的细胞因子形成一个动态调控网络，而分化受T-bet和GATA-3两个主要基因位点调控。我们基于T-bet和GATA-3在t辅助细胞分化过程中的基因表达水平，建立了一个系统动力学模型来模拟t辅助细胞的分化和再分化过程。我们得出了模型的三种终极状态，并得出只要系统动力学处于不稳定平衡点，细胞分化潜能就存在的结论；当模型达到一个稳定的平衡点时，辅助t细胞将不再具有分化的潜力。此外，转录因子表达的时滞会导致分化过程中细胞因子分泌的振荡。
In the human immune system, T-helper cells are able to differentiate into two lymphocyte subsets: Th1 and Th2. The intracellular signaling pathways of differentiation form a dynamic regulation network by secreting distinctive types of cytokines, while differentiation is regulated by two major gene loci: T-bet and GATA-3. We developed a system dynamics model to simulate the differentiation and re-differentiation process of T-helper cells, based on gene expression levels of T-bet and GATA-3 during differentiation of these cells. We arrived at three ultimate states of the model and came to the conclusion that cell differentiation potential exists as long as the system dynamics is at an unstable equilibrium point; the T-helper cells will no longer have the potential of differentiation when the model reaches a stable equilibrium point. In addition, the time lag caused by expression of transcription factors can lead to oscillations in the secretion of cytokines during differentiation.