GSE136679
Functional Compensation Precedes Recovery of Tissue Mass Following Acute Liver Injury
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/b-catenin signaling. Interestingly, transcriptional compensation is most prominent in non-proliferating cells, clearly delineating two separate phases of liver recovery. Overall, our work describes a new mechanism by which the liver maintains essential physiological functions prior to cellular reconstitution and characterizes macrophage-derived WNT signals required for this compensation. Overall design: Examination by single-cell RNA-Seq of hepatocyte response to acute liver injury at multiple time points in an acetaminophen toxicity and a partial hepatectomy injury model. Untreated controls are also included.