IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-19558-3.html
   My bibliography  Save this article

Functional compensation precedes recovery of tissue mass following acute liver injury

Author

Listed:
  • Chad M. Walesky

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Kellie E. Kolb

    (Institute of Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Ragon Institute of MGH, MIT and Harvard)

  • Carolyn L. Winston

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Jake Henderson

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Benjamin Kruft

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Ira Fleming

    (Institute of Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Ragon Institute of MGH, MIT and Harvard)

  • Sungjin Ko

    (University of Pittsburgh, School of Medicine; and Pittsburgh Liver Research Center, University of Pittsburgh and University of Pittsburgh Medical Center)

  • Satdarshan P. Monga

    (University of Pittsburgh, School of Medicine; and Pittsburgh Liver Research Center, University of Pittsburgh and University of Pittsburgh Medical Center)

  • Florian Mueller

    (Imaging and Modeling Unit, Institut Pasteur, UMR 3691CNRS, C3BI USR 3756 IP CNRS)

  • Udayan Apte

    (Toxicology, and Therapeutics, University of Kansas Medical Center)

  • Alex K. Shalek

    (Institute of Medical Engineering & Science (IMES), Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard
    Ragon Institute of MGH, MIT and Harvard
    Harvard-MIT Division of Health Sciences and Technology)

  • Wolfram Goessling

    (Brigham and Women’s Hospital, Harvard Medical School
    Broad Institute of MIT and Harvard
    Harvard-MIT Division of Health Sciences and Technology
    Dana-Farber Cancer Institute)

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.

Suggested Citation

  • Chad M. Walesky & Kellie E. Kolb & Carolyn L. Winston & Jake Henderson & Benjamin Kruft & Ira Fleming & Sungjin Ko & Satdarshan P. Monga & Florian Mueller & Udayan Apte & Alex K. Shalek & Wolfram Goes, 2020. "Functional compensation precedes recovery of tissue mass following acute liver injury," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19558-3
    DOI: 10.1038/s41467-020-19558-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-19558-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-19558-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rui Wang & Youwei Chen & Jiazhen Han & Huikang Ye & Huiran Yang & Qianyan Li & Yizhen He & Boyu Ma & Junjie Zhang & Yanli Ge & Zhe Wang & Bo Sun & Huahua Liu & Liming Cheng & Zhirong Wang & Gufa Lin, 2024. "Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19558-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.