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Resolving the graft ischemia-reperfusion injury during liver transplantation at the single cell resolution
bioRxiv - Cell Biology Pub Date : 2021-01-10 , DOI: 10.1101/2021.01.10.426087
Linhe Wang , Jie Li , Shuai He , Haitian Chen , Shujiao He , Meixian Yin , DaWei Zou , Jinghong Xu , Shirui Chen , Tao Luo , Xinyu Yu , Jinxin Bei , Zhiyong Guo , Xiaoshun He

Ischemia-reperfusion injury (IRI) remains the major reason for impaired donor graft function and increased mortality post-liver transplantation. The mechanism of IRI involves multiple pathophysiological processes and numerous types of cells. However, a systematic and comprehensive single-cell transcriptional profile of intrahepatic cells during liver transplantation is still unclear. We performed a single-cell transcriptome analysis of 14,313 cells from liver tissues collected from pre-procurement, at the end of preservation and 2 h post-reperfusion. We made detailed annotations of mononuclear phagocyte, endothelial cell, NK/T, B and plasma cell clusters, and we described the dynamic changes of the transcriptome of these clusters during IRI and the interaction between mononuclear phagocyte clusters and other cell clusters. In addition, we found that TNFAIP3 interacting protein 3 (TNIP3), specifically and highly expressed in Kupffer cell clusters post-reperfusion, may have a protective effect on IRI. In summary, our study provides the first dynamic transcriptome map of intrahepatic cell clusters during liver transplantation at single-cell resolution.

中文翻译:

以单细胞分辨率解决肝移植过程中的移植物缺血再灌注损伤

缺血再灌注损伤(IRI)仍然是供体移植物功能受损和肝移植后死亡率增加的主要原因。IRI的机制涉及多种病理生理过程和多种类型的细胞。但是,尚不清楚肝移植过程中肝内细胞的系统和全面的单细胞转录谱。我们对保存前和再灌注后2小时从手术前收集的肝脏组织中的14,313个细胞进行了单细胞转录组分析。我们对单核吞噬细胞,内皮细胞,NK / T,B和浆细胞簇进行了详细注释,并描述了IRI期间这些簇的转录组的动态变化以及单核吞噬细胞簇与其他细胞簇之间的相互作用。此外,我们发现TNFAIP3相互作用蛋白3(TNIP3),特别是在再灌注后在库普弗细胞簇中高表达,可能对IRI有保护作用。总而言之,我们的研究提供了肝移植过程中单细胞分辨率下肝内细胞簇的第一个动态转录组图。
更新日期:2021-01-11
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