Single-cell profiling reveals distinct immune phenotypes that contribute to ischaemia-reperfusion injury after steatotic liver transplantation.
Single-cell profiling reveals distinct immune phenotypes that contribute to ischaemia-reperfusion injury after steatotic liver transplantation.
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单细胞分析揭示了不同的免疫表型有助于脂肪变性肝移植后缺血-再灌注损伤。
DOI：
10.1111/cpr.13116
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发表时间：
2021-10
影响因子：
8.5
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Yang X;Lu D;Wang R;Lian Z;Lin Z;Zhuo J;Chen H;Yang M;Tan W;Yang M;Wei X;Wei Q;Zheng S;Xu X
器官供需矛盾导致脂肪变性肝脏用于肝移植的比例越来越高。然而，肝脏脂肪变性是移植失败的主要风险因素，因为移植期间对缺血再灌注（I/R）损伤的易感性增加。为了在单细胞水平上评估脂肪变性肝移植物微环境中免疫细胞的可塑性和表型，对来自移植大鼠肝脏的23 675个细胞进行了单细胞RNA测序（scRNA-Seq）。进行生物信息学分析和多重免疫组织化学以评估不同细胞亚型的功能特性、转录调控、表型转换和细胞间相互作用。我们已经在移植的肝脏中鉴定出11种不同的细胞类型，并发现高度复杂的生态系统是由髓源性细胞亚群形成的，这些细胞亚群在不同状态之间转换并相互作用。值得注意的是，在移植的脂肪变性肝脏中富集的具有高表达集落刺激因子3（CSF 3）的库普弗细胞（KC）的促炎表型可能参与脂肪移植物损伤。我们还检测到一个树突状细胞（DC）亚群，其具有与CD 8 + T细胞相关的高表达XCR 1，介导I/R损伤引起的更严重的脂肪性肝损伤。我们的研究结果为脂肪变性加重I/R损伤所致肝损伤的机制提供了新的见解。基于这些观察结果的干预措施为减轻脂肪肝移植损伤和扩大供体库创造了机会。样品制备、测序和生物信息学分析的工作流程示意图。
The discrepancy between supply and demand of organ has led to an increased utilization of steatotic liver for liver transplantation (LT). Hepatic steatosis, however, is a major risk factor for graft failure due to increased susceptibility to ischaemia‐reperfusion (I/R) injury during transplantation. To assess the plasticity and phenotype of immune cells within the microenvironment of steatotic liver graft at single‐cell level, single‐cell RNA‐sequencing (scRNA‐Seq) was carried out on 23 675 cells from transplanted rat livers. Bioinformatic analyses and multiplex immunohistochemistry were performed to assess the functional properties, transcriptional regulation, phenotypic switching and cell‐cell interactions of different cell subtypes. We have identified 11 different cell types in transplanted livers and found that the highly complex ecosystem was shaped by myeloid‐derived cell subsets that transit between different states and interact mutually. Notably, a pro‐inflammatory phenotype of Kupffer cells (KCs) with high expression of colony‐stimulating factor 3 (CSF3) that was enriched in transplanted steatotic livers was potentially participated in fatty graft injury. We have also detected a subset of dendritic cells (DCs) with highly expressing XCR1 that was correlated with CD8+ T cells, mediating the severer steatotic liver damage by I/R injury. The findings of our study provide new insight into the mechanisms by which steatosis exacerbates liver damage from I/R injury. Interventions based on these observations create opportunities in attenuating fatty liver graft injury and expanding the donor pool. The schematic of workflow for the sample preparation, sequencing and bioinformatic analysis.
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影响因子：
16.6
作者：
MacParland SA;Liu JC;Ma XZ;Innes BT;Bartczak AM;Gage BK;Manuel J;Khuu N;Echeverri J;Linares I;Gupta R;Cheng ML;Liu LY;Camat D;Chung SW;Seliga RK;Shao Z;Lee E;Ogawa S;Ogawa M;Wilson MD;Fish JE;Selzner M;Ghanekar A;Grant D;Greig P;Sapisochin G;Selzner N;Winegarden N;Adeyi O;Keller G;Bader GD;McGilvray ID
通讯作者：
McGilvray ID
影响因子：
29.4
作者：
Cotter, Thomas G.;Rinella, Mary
通讯作者：
Rinella, Mary
影响因子：
6
作者：
Chen, Jiqiu;Chemaly, Elie;Tarzami, Sima T.
通讯作者：
Tarzami, Sima T.
影响因子：
24.5
作者：
Krenkel, Oliver;Hundertmark, Jana;Tacke, Frank
通讯作者：
Tacke, Frank
影响因子：
64.8
作者：
Dudek, Michael;Pfister, Dominik;Knolle, Percy A.
通讯作者：
Knolle, Percy A.