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Isolation of Nuclei from Flash-Frozen Liver Tissue for Single-Cell Multiomics
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Decoding Single-cell Landscape and Intercellular Crosstalk in the Transplanted Liver.

Haitao Huang1,2, Ruihan Chen1,2, Yimou Lin1,2

  • 1Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Transplantation
|November 22, 2022
PubMed
Summary

This study reveals the cellular dynamics of transplanted livers, showing immune cell replacement and the potential for recipient cells to become tissue-resident. This provides insights into graft recovery and crosstalk after liver transplantation (LT).

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Area of Science:

  • Immunology
  • Transplantation Biology
  • Single-cell Genomics

Background:

  • Liver transplantation (LT) is a critical treatment for end-stage liver disease.
  • Understanding graft reconstruction and cellular crosstalk post-LT remains challenging due to biological complexity.

Purpose of the Study:

  • To investigate the physiological processes of graft recovery and intercellular crosstalk following LT.
  • To create a detailed cellular atlas of the transplanted liver.

Main Methods:

  • Establishment of an immune-tolerated orthotopic LT mouse model.
  • Application of single-cell RNA sequencing and CyTOF for comprehensive cellular analysis.

Main Results:

  • Identification of acute and stable phases in perioperative graft recovery.
  • Detailed annotation of the transplanted liver's cellular landscape and dynamic cell modifications.
  • Discovery that recipient immune cells largely replace graft cells, with notable exceptions of specific macrophage and natural killer cell populations exhibiting tissue-resident potential.

Conclusions:

  • Delineation of a comprehensive cell atlas (type, proportion, source, time) for the transplanted liver.
  • Elucidation of graft reconstruction mechanisms and graft-recipient cellular crosstalk.
  • Highlighting the potential for recipient-derived cells to differentiate into tissue-resident populations post-LT, influencing liver remodeling.