Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics Representation (ADViSOR).
Defining spatiotemporal gene modules in liver regeneration using Analytical Dynamic Visual Spatial Omics Representation (ADViSOR).
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DOI：
10.1097/hc9.0000000000000289
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发表时间：
2023-11-01
影响因子：
5.1
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中科院分区：
文献类型：
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作者：
肝脏是手术或毒性损伤后唯一具有再生能力的器官，肝部分切除术可作为肝再生（LR）的实验模型。肝部分切除术后，基因表达从门静脉周围到中心周围发生动态变化；因此，空间转录组学与一种新的计算管道（ADViSOR[分析动态视觉空间组学表示]）相结合，被用来深入了解LR的时空分子基础。ADViSOR包括时间间隔主成分分析和滑动动态超图，应用于通过LR连续分析的100个基因的空间转录组学数据，包括部分肝切除术后关键时间点的Wnt/β-catenin通路的关键成分。该计算管道确定了展示细胞信号传导和细胞间相互作用的关键功能模块，推断了共享的调节机制。具体来说，ADViSOR分析表明巨噬细胞介导的炎症是早期LR的关键组成部分，并证实了先前的研究表明Ccnd1是一种肝细胞增殖基因，受Wnt/β-catenin通路的调节。这些发现随后通过蛋白质定位得到了验证，这为LR期间Wnt/β-catenin通路的时空变化提供了进一步的证实和新的见解。因此，ADViSOR可能会在其他复杂的时空环境中产生新的见解。
The liver is the only organ with the ability to regenerate following surgical or toxicant insults, and partial hepatectomy serves as an experimental model of liver regeneration (LR). Dynamic changes in gene expression occur from the periportal to pericentral regions of the liver following partial hepatectomy; thus, spatial transcriptomics, combined with a novel computational pipeline (ADViSOR [Analytic Dynamic Visual Spatial Omics Representation]), was employed to gain insights into the spatiotemporal molecular underpinnings of LR. ADViSOR, comprising Time-Interval Principal Component Analysis and sliding dynamic hypergraphs, was applied to spatial transcriptomics data on 100 genes assayed serially through LR, including key components of the Wnt/β-catenin pathway at critical timepoints after partial hepatectomy. This computational pipeline identified key functional modules demonstrating cell signaling and cell-cell interactions, inferring shared regulatory mechanisms. Specifically, ADViSOR analysis suggested that macrophage-mediated inflammation is a critical component of early LR and confirmed prior studies showing that Ccnd1, a hepatocyte proliferative gene, is regulated by the Wnt/β-catenin pathway. These findings were subsequently validated through protein localization, which provided further confirmation and novel insights into the spatiotemporal changes in the Wnt/β-catenin pathway during LR. Thus, ADViSOR may yield novel insights in other complex, spatiotemporal contexts.
使用计算模型推断实验性创伤/失血性休克和复苏中组织特异性、TLR4 依赖性 17 型免疫相互作用。
影响因子：
7.3
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通讯作者：
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影响因子：
4.4
作者：
Liu, Yujian;Yuan, Youzhong;Li, Yuehua;Zhang, Jian;Xiao, Guozhi;Vodovotz, Yoram;Billiar, Timothy R.;Wilson, Mark A.;Fan, Jie
通讯作者：
Fan, Jie