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© Research
Publication : Nature communications

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 19 Nov 2020

Walesky CM, Kolb KE, Winston CL, Henderson J, Kruft B, Fleming I, Ko S, Monga SP, Mueller F, Apte U, Shalek AK, Goessling W,

Link to Pubmed [PMID] – 33214549

Link to DOI – 10.1038/s41467-020-19558-3

Nat Commun 2020 11; 11(1): 5785

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.

https://pubmed.ncbi.nlm.nih.gov/33214549