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research article

Mice with humanized livers reveal the role of hepatocyte clocks in rhythmic behavior

Delbes, Anne-Sophie
•
Quinones, Mar
•
Gobet, Cedric  
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May 19, 2023
Science Advances

The synchronization of circadian clock depends on a central pacemaker located in the suprachiasmatic nuclei. However, the potential feedback of peripheral signals on the central clock remains poorly characterized. To explore whether peripheral organ circadian clocks may affect the central pacemaker, we used a chimeric model in which mouse hepatocytes were replaced by human hepatocytes. Liver humanization led to reprogrammed diurnal gene expression and advanced the phase of the liver circadian clock that extended to muscle and the entire rhythmic physiology. Similar to clock-deficient mice, liver-humanized mice shifted their rhythmic physiology more rapidly to the light phase under day feeding. Our results indicate that hepatocyte clocks can affect the central pacemaker and offer potential perspectives to apprehend pathologies associated with altered circadian physiology.

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Type
research article
DOI
10.1126/sciadv.adf2982
Web of Science ID

WOS:000996685800008

Author(s)
Delbes, Anne-Sophie
•
Quinones, Mar
•
Gobet, Cedric  
•
Castel, Julien
•
Denis, Raphael G. P.
•
Berthelet, Jeremy
•
Weger, Benjamin D.
•
Challet, Etienne
•
Charpagne, Aline
•
Metairon, Sylviane
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Date Issued

2023-05-19

Publisher

AMER ASSOC ADVANCEMENT SCIENCE

Published in
Science Advances
Volume

9

Issue

20

Article Number

eadf2982

Subjects

Multidisciplinary Sciences

•

Science & Technology - Other Topics

•

circadian behavior

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consequences

•

coordination

•

metabolism

•

insights

•

obesity

•

growth

Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPNAE  
Available on Infoscience
July 31, 2023
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/199575
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