An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver
An extensive and dynamic trans-omic network illustrating prominent regulatory mechanisms in response to insulin in the liver
复制标题
广泛且动态的跨组学网络说明了肝脏中胰岛素反应的显着调节机制
DOI：
10.1016/j.celrep.2021.109569
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发表时间：
2021
期刊：
影响因子：
8.8
通讯作者：
Kubota Hiroyuki
中科院分区：
文献类型：
--
作者：
Matsuzaki Fumiko;Uda Shinsuke;Yamauchi Yukiyo;Matsumoto Masaki;Soga Tomoyoshi;Maehara Kazumitsu;Ohkawa Yasuyuki;Nakayama Keiichi I.;Kuroda Shinya;Kubota Hiroyuki
多组数据的有效结合可以增强我们对复杂生物现象的理解。为了构建一个具有多个组层的上下文相关网络，即跨组学网络，我们对胰岛素注射后4小时的小鼠肝脏进行了磷酸蛋白质组学、转录组学、蛋白质组学和代谢组学，并整合了所得到的时间序列。分析了该网络的结构特征和动态性质，以阐明胰岛素的影响。蛋白质磷酸化的早期和显著变化，以及通过非转录机制在mRNA和蛋白质水平上的持续和非同步变化，表明磷酸化介导的信号和蛋白质表达调控之间的串扰增强。代谢反应表现出不同的时间调节，不同类别的代谢反应在早期时间点瞬时增加，而氨基酸和核苷酸类别的反应在后期由于过程趋同而增强。这种广泛的和动态的跨体组网络的观点阐明了通过错综复杂的层间协调来驱动胰岛素反应的重要调节机制。
An effective combination of multi-omic datasets can enhance our understanding of complex biological phenomena. To build a context-dependent network with multiple omic layers, i.e., a trans-omic network, we perform phosphoproteomics, transcriptomics, proteomics, and metabolomics of murine liver for 4 h after insulin administration and integrate the resulting time series. Structural characteristics and dynamic nature of the network are analyzed to elucidate the impact of insulin. Early and prominent changes in protein phosphorylation and persistent and asynchronous changes in mRNA and protein levels through non-transcriptional mechanisms indicate enhanced crosstalk between phosphorylation-mediated signaling and protein expression regulation. Metabolic response shows different temporal regulation with transient increases at early time points across categories and enhanced response in the amino acid and nucleotide categories at later time points as a result of process convergence. This extensive and dynamic view of the trans-omic network elucidates prominent regulatory mechanisms that drive insulin responses through intricate interlayer coordination.