Functional compensation precedes recovery of tissue mass following acute liver injury.

Nature Communications
Chad WaleskyWolfram Goessling

Abstract

The liver plays a central role in metabolism, protein synthesis and detoxification. It possesses unique regenerative capacity upon injury. While many factors regulating cellular proliferation during liver repair have been identified, the mechanisms by which the injured liver maintains vital functions prior to tissue recovery are unknown. Here, we identify a new phase of functional compensation following acute liver injury that occurs prior to cellular proliferation. By coupling single-cell RNA-seq with in situ transcriptional analyses in two independent murine liver injury models, we discover adaptive reprogramming to ensure expression of both injury response and core liver function genes dependent on macrophage-derived WNT/β-catenin signaling. Interestingly, transcriptional compensation is most prominent in non-proliferating cells, clearly delineating two temporally distinct phases of liver recovery. Overall, our work describes a mechanism by which the liver maintains essential physiological functions prior to cellular reconstitution and characterizes macrophage-derived WNT signals required for this compensation.

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Citations

May 1, 2021·Cancers·Yekaterina KrutsenkoSatdarshan P Monga
Mar 24, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tianyi Chen, Anna Mae Diehl
Jan 22, 2021·Gene Expression·Shikai Hu, Satdarshan P Monga

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Methods Mentioned

BETA
surgical resection
RNA-seq
scRNA-Seq
smFISH
Seq-Well

Software Mentioned

Seurat
Well
NextSeq
GraphPad Prism
Seurat R package
R
Seq
STAR
Python
Elements

Related Concepts

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