Space-time logic of liver gene expression at sub-lobular scale.
Algorithms
Amino Acids
/ metabolism
Animals
Carbohydrate Metabolism
/ genetics
Circadian Clocks
/ genetics
Gene Expression
/ physiology
Gene Expression Profiling
Hepatocytes
/ metabolism
Lipid Metabolism
/ genetics
Liver
/ metabolism
Male
Mice
Mice, Inbred C57BL
Molecular Chaperones
/ metabolism
Period Circadian Proteins
/ genetics
Periodicity
RNA, Messenger
/ biosynthesis
Wnt Signaling Pathway
/ genetics
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
05
03
2020
accepted:
12
11
2020
pubmed:
13
1
2021
medline:
23
2
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. However, liver zonation has previously been analysed as a static phenomenon, and liver chronobiology has been analysed at tissue-level resolution. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Using mixed-effect models of messenger RNA expression and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, and most of them show multiplicative space-time effects. Such dually regulated genes cover not only key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also previously unassociated processes involving protein chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our scRNA-seq analysis reveals how liver function is compartmentalized spatio-temporally at the sub-lobular scale.
Identifiants
pubmed: 33432202
doi: 10.1038/s42255-020-00323-1
pii: 10.1038/s42255-020-00323-1
pmc: PMC7116850
mid: EMS114743
doi:
Substances chimiques
Amino Acids
0
Molecular Chaperones
0
Period Circadian Proteins
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
43-58Subventions
Organisme : Swiss National Science Foundation
ID : 173079
Pays : Switzerland
Organisme : European Research Council
ID : 768956
Pays : International
Organisme : Howard Hughes Medical Institute
Pays : United States
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