Functional compensation precedes recovery of tissue mass following acute liver injury
Name
s41467-020-19558-3.pdf
Description
Published version
Size
6 MB
Format
Adobe PDF
Checksum (MD5)
000f2ca164e96eb3cd73ae96b9ca5d77
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
Date Issued
2020
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
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-020-19558-3
