Department of Zoology, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8502, Japan.
Faculty of Informatics, The University of Fukuchiyama, 3370 Hori, Fukuchiyama, Kyoto, 620-0886, Japan.
Sci Rep. 2021 Feb 17;11(1):4001. doi: 10.1038/s41598-021-83045-y.
Linkage logic theory provides a mathematical criterion to control network dynamics by manipulating activities of a subset of network nodes, which are collectively called a feedback vertex set (FVS). Because many biological functions emerge from dynamics of biological networks, this theory provides a promising tool for controlling biological functions. By manipulating the activity of FVS molecules identified in a gene regulatory network (GRN) for fate specification of seven tissues in ascidian embryos, we previously succeeded in reproducing six of the seven cell types. Simultaneously, we discovered that the experimentally reconstituted GRN lacked information sufficient to reproduce muscle cells. Here, we utilized linkage logic theory as a tool to find missing edges in the GRN. Then, we identified a FVS from an updated version of the GRN and confirmed that manipulating the activity of this FVS was sufficient to induce all seven cell types, even in a multi-cellular environment. Thus, linkage logic theory provides tools to find missing edges in experimentally reconstituted networks, to determine whether reconstituted networks contain sufficient information to fulfil expected functions, and to reprogram cell fate.
链接逻辑理论通过操纵网络节点子集的活动（称为反馈顶点集，FVS），为控制网络动态提供了一种数学标准。由于许多生物学功能都源自生物网络的动态，因此该理论为控制生物学功能提供了一种很有前景的工具。我们曾利用链接逻辑理论，通过操纵在海鞘胚胎中指定七种组织命运的基因调控网络（GRN）中鉴定的 FVS 分子的活性，成功复制了六种细胞类型。同时，我们发现实验重建的 GRN 缺乏足以复制肌肉细胞的信息。在这里，我们将链接逻辑理论用作寻找 GRN 中缺失边的工具。然后，我们从更新的 GRN 版本中确定了一个 FVS，并证实了操纵该 FVS 的活性足以诱导所有七种细胞类型，即使在多细胞环境中也是如此。因此，链接逻辑理论为寻找实验重建网络中缺失的边、确定重建网络是否包含足够的信息来实现预期的功能以及重新编程细胞命运提供了工具。
