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bioRxiv · 10.1101/2021.01.06.425562

Decoding the single-cell landscape and intercellular crosstalk in the transplanted liver: a 4-dimension mouse model

Huang, H.·Zhang, X.·Chen, H.·Feng, S.·Zhang, C.·Chen, R.·Lin, Y.·Ji, Q.·Ling, Q.
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Abstract

Graft remodeling after transplantation maintains graft functionality and determines graft survival. However, a comprehensive understanding of cellular diversity and interplay during graft remodeling remains to be fully characterized. In this study, we established a well tolerant C57BL/6 to C57BL/6 orthotopic liver transplantation (LT) mice model and observed two stages of graft recovery including an acute phase and a steady phase. We next performed single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) and recorded the cellular hierarchy in the transplanted liver during the two stages. Besides the dynamic change of cell proportion, it was notable that recipient-derived cells took over the transplanted liver in most cell types (e.g., B cells, T cells, dendritic cells, granulocytes and monocytes) except CD206+ MerTK+ macrophages and CD161+ CD49a+ CD49b-natural killer cells. We then focused on macrophages and captured 5 distinct transcriptional signatures to define novel subclusters. Using a ligand-receptor interaction strategy, we identified specific macrophage-hepatocyte interactions during the acute and stable phases, causing metabolic remodeling in the transplanted liver. Our results delineated a 4-dimension cell atlas (type-proportion-source-time) of the transplanted liver, which sheds light on the physiological process of liver graft maintenance and graft-recipient crosstalk.

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Huang, H., Zhang, X., Chen, H., Feng, S., Zhang, C., Chen, R., Lin, Y., Ji, Q., Ling, Q.. 2021-01-09. Decoding the single-cell landscape and intercellular crosstalk in the transplanted liver: a 4-dimension mouse model. https://doi.org/10.1101/2021.01.06.425562

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