Kobayashi Taeko, Mizuno Hiroaki, Imayoshi Itaru, Furusawa Chikara, Shirahige Katsuhiko, Kageyama Ryoichiro
Institute for Virus Research, Kyoto University, Kyoto, Japan.
Genes Dev. 2009 Aug 15;23(16):1870-5. doi: 10.1101/gad.1823109.
Stem cells do not all respond the same way, but the mechanisms underlying this heterogeneity are not well understood. Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells. Those expressing low and high levels of Hes1 tended to differentiate into neural and mesodermal cells, respectively. Furthermore, inactivation of Hes1 facilitated neural differentiation more uniformly at earlier time. Thus, Hes1-null ES cells display less heterogeneity in both the differentiation timing and fate choice, suggesting that the cyclic gene Hes1 contributes to heterogeneous responses of ES cells even under the same environmental conditions.
干细胞并非都以相同方式做出反应，但其异质性背后的机制尚未得到充分理解。在此，我们发现Hes1及其下游基因在小鼠胚胎干细胞（ES细胞）中呈振荡表达。表达低水平和高水平Hes1的细胞分别倾向于分化为神经细胞和中胚层细胞。此外，在早期阶段，Hes1的失活更均匀地促进了神经分化。因此，Hes1基因敲除的ES细胞在分化时间和命运选择上均表现出较低的异质性，这表明即使在相同环境条件下，循环基因Hes1也会导致ES细胞产生异质性反应。
