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A time- and space-resolved nuclear receptor atlas in mouse liver
in Journal of Molecular EndocrinologyThe functional versatility of the liver is paramount for organismal homeostasis. Adult liver functions are controlled by a tightly regulated transcription factor network including nuclear receptors (NRs), which orchestrate many aspects of hepatic physiology. NRs are transcription factors sensitive to extracellular cues such as hormones, lipids, xenobiotics, etc. and are modulated by intracellular signaling pathways. While liver functional zonation and adaptability to fluctuating conditions rely on a sophisticated cellular architecture, a comprehensive knowledge of NR functions within liver cell populations is still lacking. As a step toward the accurate mapping of NR functions in the liver, we characterized their levels of expression in the whole liver from C57Bl6/J male mice as a function of time and diet. Nr1d1 (Rev-erba), Nr1d2 (Rev-erbb), Nr1c2 (Pparb/d), and Nr1f3 (Rorg) exhibited a robust cyclical expression in ad libitum-fed mice which was, like most cyclically expressed NRs, reinforced upon time-restricted feeding. In a few instances, cyclical expression was lost or gained as a function of the feeding regimen. NR isoform expression was explored in purified hepatocytes, cholangiocytes, Kupffer cells, hepatic stellate cells, and liver sinusoidal cells. The expression of some NR isoforms, such as Nr1h4 (Fxra) and Nr1b1 (Rara) isoforms, was markedly restricted to a few cell types. Leveraging liver single-cell RNAseq studies yielded a zonation pattern of NRs in hepatocytes, liver sinusoidal cells, and stellate cells, establishing a link between NR subtissular localization and liver functional specialization. In summary, we provide here an up-to-date compendium of NR expression in mouse liver in space and time.
Supplementary Materials
- Supplementary Material
- Supplemental Table 1. List of primers used in RT-qPCR experiments.
- Supplemental Table 2. JTK_cycle output. Time-dependent transcriptomic data were analyzed using the JTK_cycle R script. Sheet 1: JTK_cycle output for whole liver from ad libitum-fed (AdLib) mice. Sheet 2: JTK_cycle output for whole liver from time-restricted-fed (TRF) mice.
- Supplemental Table 3. NR gene counts and NR isoform description. Sheet 1: Normalized average (n=3) RPKMs are indicated for each mouse NR. The color scale compares NR expression level between cell types (from white, no expression to red, highest expression), numbers are the averaged RPKM.
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Online ISSN: 1479-6813
Print ISSN: 0952-5041
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