Cell Type-Specific Functions of Genes Revealed by Novel Adipocyte and Hepatocyte Circadian Clock Models

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Various aspects of our daily rhythms in physiology and behavior such as the sleep-wake cycle are regulated by endogenous circadian clocks that are present in nearly every cell. It is generally accepted that these oscillators share a similar biochemical negative feedback mechanism, consisting of transcriptional activators and repressors. In this study, we developed cell-autonomous, metabolically relevant clock models in mouse hepatocytes and adipocytes. Each clock model has an integrated luciferase reporter that allows for kinetic luminescence recording with an inexpensive microplate reader and thus is feasible for most laboratories. These models are amenable to high throughput screening of small molecules or genomic entities for impacts on cell-autonomous clocks relevant to metabolism. We validated these new models by RNA interference via lentivirus-mediated knockdown of known clock genes. As expected, we found that many core clock components have similar functions across cell types. To our surprise, however, we also uncovered previously under-appreciated cell type-specific functions of core clock genes, particularly Per1, Per2, and Per3. Because the circadian system is integrated with, and influenced by, the local physiology that is under its control, our studies provide important implications for future studies into cell type-specific mechanisms of various circadian systems.

Vyšlo v časopise: Cell Type-Specific Functions of Genes Revealed by Novel Adipocyte and Hepatocyte Circadian Clock Models. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004244
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004244

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