人移植肝脏的单细胞分析确定了与早期同种异体移植功能障碍（EAD）相关的致病细胞模块

Liver transplantation (LT) is the standard therapy for the patients with end-stage liver disease. Although the technology of LT has made enormous progress in recent decades, the early allograft dysfunction (EAD) caused by ischemia-reperfusion (IR) injury still poses a huge challenge to the prognosis of recipients and organ shortage, which is a major issue that needs to be solved urgently. Nevertheless, the cellular characteristics associated with EAD are still unclear at a single-cell level. Here, we constructed a single-cell transcriptomic atlas of 58,243 liver cells from 4 donors and 4 recipient patients. These cell clusters were annotated into 14 cell types, including hepatocytes and various liver non-parenchymal cells. We found that the cell status of T/NK cells, neutrophils, monocytes, macrophages, and endothelial cells changed significantly after LT, and then we determined cell subtypes including CD8+ GZMB+ T cell, GZMB+GZMK+ NK cell, NKT cell, FOS+ monocyte, and S100A12+ neutrophil, all of which have a significant increase in cell proportion after LT. More importantly, we identified and validated that MAIT cell, GZMB+GZMK+ NK cell, and S100A12+ neutrophil as a pathogenic cellular module is highly correlated with EAD. In addition, this cellular module aggravated endothelial cell/hepatocyte injury in EAD patient through unique ligand-receptor pairs. Our findings clarified the cellular characteristics of transplanted livers and EAD-associated pathogenic cellular module at a single-cell level, bringing a new direction for prevention and treatment of EAD.