Wu Chia-Chou, Lin Che, Chen Bor-Sen
Control and Systems Biology Laboratory, National Tsing Hua University, Hsinchu 30013, Taiwan.
Institute of Communication, National Tsing Hua University, Hsinchu 30013, Taiwan.
Stem Cells Int. 2015;2015:792843. doi: 10.1155/2015/792843. Epub 2015 Apr 21.
The induction of stem cells toward a desired differentiation direction is required for the advancement of stem cell-based therapies. Despite successful demonstrations of the control of differentiation direction, the effective use of stem cell-based therapies suffers from a lack of systematic knowledge regarding the mechanisms underlying directed differentiation. Using dynamic modeling and the temporal microarray data of three differentiation stages, three dynamic protein-protein interaction networks were constructed. The interaction difference networks derived from the constructed networks systematically delineated the evolution of interaction variations and the underlying mechanisms. A proposed relevance score identified the essential components in the directed differentiation. Inspection of well-known proteins and functional modules in the directed differentiation showed the plausibility of the proposed relevance score, with the higher scores of several proteins and function modules indicating their essential roles in the directed differentiation. During the differentiation process, the proteins and functional modules with higher relevance scores also became more specific to the neuronal identity. Ultimately, the essential components revealed by the relevance scores may play a role in controlling the direction of differentiation. In addition, these components may serve as a starting point for understanding the systematic mechanisms of directed differentiation and for increasing the efficiency of stem cell-based therapies.
为推动基于干细胞的疗法发展，需要将干细胞诱导至期望的分化方向。尽管已成功证明可控制分化方向，但基于干细胞的疗法的有效应用仍因缺乏关于定向分化潜在机制的系统知识而受到阻碍。利用动态建模和三个分化阶段的时间微阵列数据，构建了三个动态蛋白质-蛋白质相互作用网络。从构建的网络中衍生出的相互作用差异网络系统地描绘了相互作用变化的演变及其潜在机制。提出的相关性评分确定了定向分化中的关键成分。对定向分化中知名蛋白质和功能模块的检查表明了所提出的相关性评分的合理性，几种蛋白质和功能模块的得分较高表明它们在定向分化中起着关键作用。在分化过程中，相关性评分较高的蛋白质和功能模块也变得对神经元特征更具特异性。最终，相关性评分揭示的关键成分可能在控制分化方向中发挥作用。此外，这些成分可作为理解定向分化系统机制和提高基于干细胞疗法效率的起点。
