MICROSCOPY Vol.47▶No.2 2012
■Feature Article: Morphology of Biological Clocks

Cell-Autonomous Formation of Mammalian Circadian Clock

Kazuhiro Yagita

Abstract: The circadian clock regulates many aspects of physiology and behavior such as sleep-wake cycles, body temperature, liver metabolism, renal activity, various hormonal secretion and cell proliferation. For the long time, it has been believed that the circadian clock oscillator exists only in the neurons of hypothalamic suprachiasmatic nucleus (SCN) where the circadian center of mammals resides. However, recently we have elucidated that even cultured cell lines involve the intrinsic self-sustained oscillating system. In addition, we also discovered that mammalian cellular circadian clock residing in our body developed cell-autonomously during the cellular differentiation process. Using bioluminescence imaging system to monitor clock gene expression, we show that the circadian bioluminescence activity rhythm is not detected in the mouse embryonic stem (ES) cells. In addition, when those differentiated cells are reprogrammed by expressing Sox2, Klf4, Oct-3/4 and c-Myc genes, those are used to generate induced pluripotent stem (iPS) cells, the circadian oscillation re-disappeared. The in vitro cellular differentiation and reprogramming system using ES cells and stem cell technology may provide a new strategy to understand the cross-talk mechanisms between circadian system and cellular differentiation system.  

Key words: circadian rhythm, clock genes, development, cell-autonomous