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.

肝移植（LT）是患有终末期肝病的个体的标准疗法。尽管 LT 技术取得了显着进步，但早期同种异体移植功能障碍 (EAD) 的发生率仍然是一个严重问题，加剧了当前的器官短缺并对受者的预后产生不利影响。不幸的是，令人困惑的肝脏异质性阻碍了对导致 EAD 的细胞特征和分子事件的表征。在此，我们构建了来自非 EAD 和 EAD 患者的人类移植肝脏的开创性单细胞转录组学景观，其中从 7 名供体的冷灌注和门静脉再灌注阶段收集了 12 个肝脏样本。比较非 EAD 和 EAD 患者的 75 231 个细胞，揭示了 EAD 相关免疫生态位，包括粘膜相关不变 T 细胞、颗粒酶 B ⁺ ( GZMB ⁺ ) 颗粒酶 K ( GZMK ⁺ ) 自然杀伤细胞和 S100 钙结合蛋白A12 ⁺ ( S100A12 ⁺ ) 中性粒细胞。此外，我们在两个独立队列中验证了这种免疫生态位及其与 EAD 发生的关联。我们的研究结果阐明了移植肝脏的细胞特征以及单细胞水平上与 EAD 相关的致病性免疫生态位，从而为 EAD 发病提供了有价值的见解。