首页|A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

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Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prog-nosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B+(GZMB+)granzyme K+(GZMK+)natu-ral killer cells,and S100 calcium binding protein A12+(S100A12+)neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings eluci-date the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Human liver transplantationEarly allograft dysfunctionPathogenic immune nicheSingle-cell analysisCell-cell communication

Xin Shao、Zheng Wang、Kai Wang、Xiaoyan Lu、Ping Zhang、Rongfang Guo、Jie Liao、Penghui Yang、Shusen Zheng、Xiao Xu、Xiaohui Fan

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Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China

National Key Laboratory of Chinese Medicine Modernization,Innovation Center of Yangtze River Delta,Zhejiang University,Jiaxing 314103,China

Zhejiang University School of Medicine,Hangzhou 310058,China

NHC Key Laboratory of Combined Multi-organ Transplantation,Hangzhou 310003,China

Department of Hepatobiliary and Pancreatic Surgery,Shulan(Hangzhou)Hospital Affiliated to Shulan International Medical College,Zhejiang Shuren University,Hangzhou 310000,China

Engineering Research Center of Innovative Anticancer Drugs,Ministry of Education,Harbin 150023,China

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National Natural Science Foundation of ChinaInnovation Team and Talents Cultivation Program of National Administration of Traditional Chinese MedicineFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central UniversitiesKey Program of National Natural Science Foundation of ChinaKey Research and Development Program of ChinaMajor Research Plan of the National Natural Science Foundation of ChinaNingbo Top Medical and Health Research Program

82200725ZYYCXTD-D-202002226-2023-00114226-2022-00226226-2023-00059819300162021YFA1100500921592022022030309

2024

10.1016/j.eng.2023.12.004

工程(英文)

工程(英文)

CSTPCDEI
ISSN：2095-8099
年,卷(期)：2024.36(5)