A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction
作者机构:Pharmaceutical Informatics InstituteCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key Laboratory of Chinese Medicine ModernizationInnovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Zhejiang University School of MedicineHangzhou 310058China NHC Key Laboratory of Combined Multi-organ TransplantationHangzhou 310003China Department of Hepatobiliary and Pancreatic SurgeryShulan(Hangzhou)Hospital Affiliated to Shulan International Medical CollegeZhejiang Shuren UniversityHangzhou 310000China Engineering Research Center of Innovative Anticancer DrugsMinistry of EducationHarbin 150023China
出 版 物:《Engineering》 (工程(英文))
年 卷 期:2024年第36卷第5期
页 面:193-208页
核心收录:
学科分类:0710[理学-生物学] 0831[工学-生物医学工程(可授工学、理学、医学学位)] 1007[医学-药学(可授医学、理学学位)] 100706[医学-药理学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100210[医学-外科学(含:普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 0836[工学-生物工程] 10[医学]
基 金:supported by the National Natural Science Foundation of China(82200725) the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002) the Fundamental Research Funds for the Central Universities(226-2023-00114,226-2022-00226,and 226-2023-00059) the Key Program of National Natural Science Foundation of China(81930016) the Key Research and Development Program of China(2021YFA1100500) the Major Research Plan of the National Natural Science Foundation of China(92159202) the Ningbo Top Medical and Health Research Program(2022030309)
主 题:Human liver transplantation Early allograft dysfunction Pathogenic immune niche Single-cell analysis Cell-cell communication
摘 要:Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver *** 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 ***,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to ***,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 *** of the 75231 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^(+))***,we verified this immune niche and its association with EAD occurrence in two independent *** 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.