Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto, Japan.
J Biol Rhythms. 2019 Oct;34(5):525-532. doi: 10.1177/0748730419865436. Epub 2019 Aug 1.
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 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.
哺乳动物的生物钟协调着各种生理功能，它在个体发育过程中逐渐形成。最近，我们报道了 CLOCK 蛋白表达的转录后抑制是小鼠发育过程中生物钟出现的关键机制。然而，是否存在一种共同的机制来调节人类生物钟的发育尚不清楚。在本研究中，我们表明人类诱导多能干细胞（iPSCs）没有明显的昼夜分子振荡。此外，与在小鼠中出现昼夜振荡所需的时间相比，人类 iPSCs 的体外分化培养需要更长的时间。未分化的人类 iPSCs 中的 CLOCK 蛋白表达受到转录后抑制，尽管 mRNA 表达，这与我们之前在小鼠胚胎干细胞、iPSCs 和早期小鼠胚胎中的观察结果一致。这些结果表明，CLOCK 蛋白的表达可能不仅在小鼠中，而且在人类的早期发育阶段也受到转录后抑制。
