Decoding Single-cell Landscape and Intercellular Crosstalk in the Transplanted Liver

作者：Haitao Huang, Ruihan Chen, Yimou Lin, Jingyu Jiang, Feng Shi, Xueyou Zhang, Cheng Zhang, Qinghua Ji, Hui Chen, Haiyang Xie, Shusen Zheng, Qi Ling · 发表于：Transplantation · 年份：2022 · DOI：10.1097/tp.0000000000004365 · 被引用次数：16 · 研究领域：Single-cell and spatial transcriptomics、Organ Transplantation Techniques and Outcomes、Liver physiology and pathology

BACKGROUND: Liver transplantation (LT) is the most effective treatment for various end-stage liver diseases. However, the cellular complexity and intercellular crosstalk of the transplanted liver have constrained analyses of graft reconstruction after LT. METHODS: We established an immune-tolerated orthotopic LT mouse model to understand the physiological process of graft recovery and intercellular crosstalk. We employed single-cell RNA sequencing and cytometry by time-of-flight to comprehensively reveal the cellular landscape. RESULTS: We identified an acute and stable phase during perioperative graft recovery. Using single-cell technology, we made detailed annotations of the cellular landscape of the transplanted liver and determined dynamic modifications of these cells during LT. We found that 96% of graft-derived immune cells were replaced by recipient-derived cells from the preoperative to the stable phase. However, CD206 + MerTK + macrophages and CD49a + CD49b - natural killer cells were composed of both graft and recipient sources even in the stable phase. Intriguingly, the transcriptional profiles of these populations exhibited tissue-resident characteristics, suggesting that recipient-derived macrophages and natural killer cells have the potential to differentiate into 'tissue-resident cells' after LT. Furthermore, we described the transcriptional characteristics of these populations and implicated their role in regulating the metabolic and immune remodeling of the t...