Oscillatory protein expression dynamics endows stem cells with robust differentiation potential.
Oscillatory protein expression dynamics endows stem cells with robust differentiation potential.
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DOI：
10.1371/journal.pone.0027232
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kaneko K
中科院分区：
文献类型：
--
作者：
Suzuki N;Furusawa C;Kaneko K
缺乏对干细胞分化和增殖的理解是发育生物学中的一个基本问题。尽管干细胞分化的基因调控网络（grn）已被部分确定，但分化动力学的本质及其调控导致稳健发育的机制仍不清楚。在此，我们使用细胞动力学系统建模方法，使用所有可能的具有少数基因的grn进行了发育过程的模拟，并筛选了可以通过细胞间相互作用产生细胞类型多样性的grn。我们发现增殖和分化的模型干细胞总是表现出振荡表达动力学，并且这种干细胞的分化频率受到调节，导致数量分布稳健。此外，我们发现了干细胞分化的共同调控基序，其中产生振荡表达动力学和稳定不同细胞状态的调控基序的组合发挥了重要作用。这些发现可以解释最近观察到的干细胞细胞状态的异质性和动态平衡，并可用于预测干细胞系统中负责分化的调节网络。
The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems.
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