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The Hepatocyte Clock and Feeding Interdependently Control Chrono-Homeostasis of Multiple Liver Cell Types (single nuclei RNA-seq)

ABSTRACT: Most cells in the body contain a cell autonomous molecular clock, but the requirement of peripheral clocks for circadian rhythmicity, and their effects on physiology, are not well understood. Here we show that deletion of core clock components REV-ERBa and b in adult mouse hepatocytes caused the loss of circadian rhythmicity of many liver genes, as expected, but also led to maintained and even gained rhythmicity of other genes without altering feeding behavior. The loss of REV-ERBs from hepatocytes leads to an exaggerated circadian rhythm of de novo lipogenesis and serum triglyceride levels. It is increasingly recognized that liver function is also influenced by non-hepatocytic cells, and remarkably the loss of REV-ERBs in hepatocytes remodeled the circadian transcriptomes of multiple cell types within the liver without altering their core clocks, indicating that hepatocytes communicated time signals to the non-hepatocytic cells. Finally, alteration of food availability, which is the dominant zeitgeber in the liver, demonstrated strong interdependence of the cell-autonomous hepatocyte clock mechanism and non-cell-autonomous environmental change. Together these studies reveal the interdependence of endogenous hepatocyte clocks and feeding entrainment on the regulation of circadian rhythms of multiple cell types in the liver.

ORGANISM(S): Mus musculus

PROVIDER: GSE143526 | GEO | 2020/07/30

REPOSITORIES: GEO

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