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Functional compensation precedes recovery of tissue mass following acute liver injury

Author(s)
Walesky, Chad M; Kolb, Kellie E; Winston, Carolyn L; Henderson, Jake; Kruft, Benjamin; Fleming, Ira; Ko, Sungjin; Monga, Satdarshan P; Mueller, Florian; Apte, Udayan; Shalek, Alex K; Goessling, Wolfram; ... Show more Show less
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Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
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Abstract
© 2020, The Author(s). 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.
Date issued
2020
URI
https://hdl.handle.net/1721.1/141275
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Walesky, Chad M, Kolb, Kellie E, Winston, Carolyn L, Henderson, Jake, Kruft, Benjamin et al. 2020. "Functional compensation precedes recovery of tissue mass following acute liver injury." Nature Communications, 11 (1).
Version: Final published version

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