 |
Journal articles
Functional compensation precedes recovery of tissue mass following acute liver injury
Chad Walesky
1
Kellie Kolb
2, 3, 4, 5
Carolyn Winston
1
Jake Henderson
1
Benjamin Kruft
1
Ira Fleming
2, 3, 4, 5
Sungjin Ko
6
Satdarshan Monga
6
Florian Mueller
7, 8
Udayan Apte
9
Alex Shalek
2, 3, 4, 10, *
Wolfram Goessling
1, 3, 10, 11, 12, 13, *
*
Corresponding author
Chad Walesky 1
Author ORCID : https://orcid.org/0000-0003-3800-3453
Kellie Kolb 2, 3, 4, 5
Author ORCID : https://orcid.org/0000-0001-8840-7363
Carolyn Winston 1
Author ORCID : https://orcid.org/0000-0003-0140-2426
Jake Henderson 1
Author ORCID : https://orcid.org/0000-0003-1981-359X
Benjamin Kruft 1
Author ORCID : https://orcid.org/0000-0001-5964-0836
Ira Fleming 2, 3, 4, 5
Author ORCID : https://orcid.org/0000-0002-4691-6933
Sungjin Ko 6
Author ORCID : https://orcid.org/0000-0002-6079-5939
Satdarshan Monga 6
Author ORCID : https://orcid.org/0000-0002-8437-3378
Florian Mueller 7, 8
Author IdHAL : florian-mueller ORCID : https://orcid.org/0000-0002-9622-4396
Udayan Apte 9
Author ORCID : https://orcid.org/0000-0002-6741-7164
Alex Shalek 2, 3, 4, 10
Correspondent author ORCID : https://orcid.org/0000-0001-5670-8778
Wolfram Goessling 1, 3, 10, 11, 12, 13
Correspondent author ORCID : https://orcid.org/0000-0001-9972-1569
1
Brigham and Women’s Hospital [Boston, MA] (75 Francis Street, Boston MA 02115 - United States)
- HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
2
IMES - Institute of Medical Engineering & Science [Cambridge, MA] (45 Carleton Street, CAMBRIDGE, MA 02142 - United States)
- MIT - Massachusetts Institute of Technology (77 Massachusetts Ave, Cambridge, MA 02139 - United States)
3
BROAD INSTITUTE - Broad Institute of MIT and Harvard (Cambridge, MA 02142 - United States)
- HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
- MIT - Massachusetts Institute of Technology (77 Massachusetts Ave, Cambridge, MA 02139 - United States)
- Massachusetts General Hospital [Boston] (55 Fruit Street Boston, MA 02114 - United States)
4
Ragon Institute of MGH, MIT and Harvard (400 Technology Square, Cambridge, MA 02139 - United States)
5
Koch Institute for Integrative Cancer Research at MIT [Cambridge, MA] (500 Main Street, Building 76, Cambridge, MA 02139-4307 - United States)
- MIT - Massachusetts Institute of Technology (77 Massachusetts Ave, Cambridge, MA 02139 - United States)
6
UPMC - University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (200 Lothrop St.
Pittsburgh, PA 15213-2582 - United States)
7
Imagerie et Modélisation - Imaging and Modeling (Département Biologie computationnelle,
Département de Biologie cellulaire et Infection,
25-28, rue du docteur Roux, 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR3691 (France)
8
C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative (25-28 rue du docteur Roux, 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : USR3756 (France)
9
Department of Pharmacology, Toxicology, and Therapeutics [Kansas City, KS, USA] (United States)
- University of Kansas Medical Center [Kansas City, KS, USA] (3901 Rainbow Boulevard, Kansas City, KS 66160 - United States)
10
Harvard-MIT Division of Health Sciences and Technology [Cambridge] (Cambridge, Massachusetts 02139 - United States)
- MIT - Massachusetts Institute of Technology (77 Massachusetts Ave, Cambridge, MA 02139 - United States)
11
Dana-Farber Cancer Institute [Boston] (450 Brookline Ave.
Boston, MA 02215 - United States)
12
HSCI - Harvard Stem Cell Institute [Cambridge, USA] (Bauer Building, Administrative Suite,
7 Divinity Avenue,
Cambridge, MA 02138 - United States)
- Harvard University [Cambridge] (Massachusetts Hall, Cambridge, MA 02138 - United States)
13
Massachusetts General Hospital [Boston, MA, USA] (55 Fruit Street, Boston, MA 02114 - United States)
- HMS - Harvard Medical School [Boston] (25 Shattuck Street Boston, MA 02115 - United States)
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/βcatenin signaling. Interestingly, transcriptional compensation is most prominent in nonproliferating 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.
Document type :
Journal articles
Complete list of metadata
https://hal-pasteur.archives-ouvertes.fr/pasteur-03648876
Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Friday, April 22, 2022 - 9:30:29 AM
Last modification on : Saturday, April 23, 2022 - 3:33:20 AM
Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Friday, April 22, 2022 - 9:30:29 AM
Last modification on : Saturday, April 23, 2022 - 3:33:20 AM
File
s41467-020-19558-3.pdf
Publication funded by an institution
Licence
Distributed under a Creative Commons Attribution 4.0 International License
Identifiers
- HAL Id : pasteur-03648876, version 1
- DOI : 10.1038/s41467-020-19558-3
- PUBMED : 33214549
- PUBMEDCENTRAL : PMC7677389
Citation
Chad Walesky, Kellie Kolb, Carolyn Winston, Jake Henderson, Benjamin Kruft, et al.. Functional compensation precedes recovery of tissue mass following acute liver injury. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.5785. ⟨10.1038/s41467-020-19558-3⟩. ⟨pasteur-03648876⟩
Metrics
Record views
7
Files downloads