Respuesta :
The center of systemic metabolic balance is the mammalian liver. Hepatocytes operate in repeated lobules in the spatially organized liver tissue, and sub-lobule zones have specific tasks.
- The interaction of the circadian clock, internal signals, and food rhythms controls the liver's broad temporal regulation.
- However, liver chronobiology has previously been examined at the tissue level, and hepatic zonation has been examined as a static phenomenon.
- Here, we study the interaction between gene regulation in space and time using single-cell RNA-seq.
- We discover that numerous genes in the liver are both zonated and rhythmic, and majority of them exhibit multiplicative space-time effects using mixed-effect models of messenger RNA expression and smFISH validations.
- These dual-regulated genes span important hepatic processes like lipid, glucose, and amino acid metabolism as well as previously unrecognized activities involving protein chaperones.
- Our findings further imply that rhythmically generated Wnt ligands from non-parenchymal cells close to the central vein could account for the rhythmic and localized expression of Wnt targets.
- The liver clock is resistant to zonation, as evidenced by the expression of core circadian clock genes in a non-zoned manner.
- Our scRNA-seq data shows how liver function is spatially and temporally partitioned at the sub-lobular scale.
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