Single-cell analysis reveals a pathogenic cellular module associated with early allograft dysfunction after liver transplantation

ABSTRACT Liver transplantation (LT) is the standard therapy for patients with end-stage liver disease. Although LT technology has markedly progressed in recent decades, early allograft dysfunction (EAD) exacerbates the current organ shortage and impacts the prognosis of recipients. However, understanding of cellular characteristics and molecular events contributing to EAD is limited. Here, a large single-cell transcriptomic atlas of transplanted livers collected from four patients is constructed, including 58,243 cells, which are classified into 14 cell types and 29 corresponding subtypes with known markers, including liver parenchymal cells and non-parenchymal cells with different cell states. Compared to the pre-LT livers, graft remodeling is noted in the post-LT livers, with marked changes in several immune cells in either cell ratios or cell states. More importantly, an EAD-associated pathogenic cellular module is identified, consisting of mucosal-associated invariant T (MAIT) cells, granzyme B (GZMB) + granzyme K (GZMK) + natural killer (NK) cells, and S100A12 + neutrophils, all of which are elevated in EAD patient after LT. This cellular module is also verified in two independent datasets. Collectively, these results reveal the cellular characteristics of transplanted livers and the EAD-associated pathogenic cellular module at the single-cell level, offering new insights into the EAD occurrence after LT.