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

Nat Commun
Authors
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.

Year of Publication
2020
Journal
Nat Commun
Volume
11
Issue
1
Pages
5785
Date Published
2020 11 19
ISSN
2041-1723
DOI
10.1038/s41467-020-19558-3
PubMed ID
33214549
PubMed Central ID
PMC7677389
Links
Grant list
R24 OD017870 / OD / NIH HHS / United States
R01 DK098414 / DK / NIDDK NIH HHS / United States
R01 DK062277 / DK / NIDDK NIH HHS / United States
P30 DK120531 / DK / NIDDK NIH HHS / United States
R01 CA204586 / CA / NCI NIH HHS / United States
F32 DK111151 / DK / NIDDK NIH HHS / United States
R01 DK090311 / DK / NIDDK NIH HHS / United States
R01 DK100287 / DK / NIDDK NIH HHS / United States
R01 DK105198 / DK / NIDDK NIH HHS / United States