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

Abstract

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 transplanted liver.

CONCLUSIONS:

In summary, this study delineated a cell atlas (type-proportion-source-time) of the transplanted liver and shed light on the physiological process of graft reconstruction and graft-recipient crosstalk.

• Authors: Haitao Huang, Ruihan Chen, Yimou Lin, Jingyu Jiang, Shi Feng, Xueyou Zhang, Cheng Zhang, Qinghua Ji, Hui Chen, Haiyang Xie, Shusen Zheng, Qi Ling
• Journal: Transplantation (Transplantation) Vol. 107 Issue 4 Pg. 890-902 (04 01 2023) ISSN: 1534-6080 [Electronic] United States
• PMID: 36413145 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Topics

• Mice
• Animals
• Liver Transplantation (adverse effects)
• End Stage Liver Disease (surgery)
• Killer Cells, Natural
• Treatment Outcome