Human Circadian Molecular Oscillation Development Using Induced Pluripotent Stem Cells

The mammalian circadian clock, which coordinates various physiological functions, develops gradually during ontogeny. Recently, we have reported the posttranscriptional suppression of CLOCK protein expression as a key mechanism of the emergence of the circadian clock during mouse development. However, whether a common mechanism regulates the development of the human circadian clock remains unclear. In the present study, we show that human induced pluripotent stem cells (iPSCs) have no discernible circadian molecular oscillation. In addition, in vitro differentiation culture of human iPSCs required a longer duration than that required in mouse for the emergence of circadian oscillations. The expression of CLOCK protein in undifferentiated human iPSCs was posttranscriptionally suppressed despite the expression of CLOCK mRNA, which is consistent with our previous observations in mouse embryonic stem cells, iPSCs, and early mouse embryos. These results suggest that CLOCK protein expressions could be posttranscriptionally suppressed in the early developmental stage not only in mice but also in humans.