A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction
Xin Shao,
Zheng Wang,
Kai Wang,
Xiaoyan Lu,
Ping Zhang,
Rongfang Guo,
Jie Liao,
Penghui Yang,
Shusen Zheng,
Xiao Xu,
Xiaohui Fan
Affiliations
Xin Shao
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
Zheng Wang
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
Kai Wang
Zhejiang University School of Medicine, Hangzhou 310058, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
Xiaoyan Lu
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
Ping Zhang
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Rongfang Guo
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Jie Liao
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
Penghui Yang
Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Shusen Zheng
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
Xiao Xu
Zhejiang University School of Medicine, Hangzhou 310058, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China; Corresponding authors.
Xiaohui Fan
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; Engineering Research Center of Innovative Anticancer Drugs, Ministry of Education, Harbin 150023, China; Corresponding authors.
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 prognosis 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+) natural 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 elucidate 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.
