College of Veterinary Medicine, Northwest A&F University, Yangling, China.
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
Acta Biochim Biophys Sin (Shanghai). 2018 Aug 1;50(8):793-799. doi: 10.1093/abbs/gmy069.
The ability to self-renew is one of the most important properties of embryonic stem (ES) cells. Pluripotin (SC1), a small molecule with high activity and low toxicity, promotes self-renewal in mouse ES cells. SC1 can noticeably change the morphology of retinoic acid (RA)-induced F9 embryonic carcinoma cells (F9 cells). However, in the long term, RA and SC1 together cause cell apoptosis. When being added after 18-24 h of RA-induced F9 cell differentiation, SC1 transitorily activated Nanog and Oct4. Both Nanog and Oct4 were downregulated when SC1 and RA were added simultaneously. On the other hand, Klf4 was continually activated when SC1 was added between 6 and 24 h. Phosphorylated Erk1/2 protein levels were reduced from 6 to 24 h, whereas unphosphorylated Erk1 protein levels remained unchanged. A higher concentration of SC1 promoted cell self-renewal by strengthening the inhibition of Erk1/2 protein phosphorylation in F9 cells. Furthermore, SC1 and RA affect global DNA methylation by influencing the expressions of methylation-associated proteins, including Dnmt3b, Dnmt3l, Tet1, Tet2, and Tet3. In conclusion, SC1 inhibits the differentiation of RA-induced F9 cells mainly by reducing the levels of phosphorylated Erk1/2 and enhancing the expression of Klf4, although it also reduces DNA methylation, which may have an additional effect on ES cell differentiation.
自我更新能力是胚胎干细胞（ES 细胞）最重要的特性之一。多潜能蛋白（SC1）是一种具有高活性和低毒性的小分子，能促进小鼠 ES 细胞的自我更新。SC1 可明显改变维甲酸（RA）诱导的 F9 胚胎癌细胞（F9 细胞）的形态。然而，长期来看，RA 和 SC1 共同作用会导致细胞凋亡。当在 RA 诱导的 F9 细胞分化后 18-24 小时加入 SC1 时，SC1 短暂激活 Nanog 和 Oct4。当同时加入 SC1 和 RA 时，Nanog 和 Oct4 下调。另一方面，当在 6-24 小时之间加入 SC1 时，Klf4 持续被激活。从 6 到 24 小时，磷酸化 Erk1/2 蛋白水平降低，而未磷酸化 Erk1 蛋白水平保持不变。较高浓度的 SC1 通过加强对 F9 细胞中 Erk1/2 蛋白磷酸化的抑制作用，促进细胞自我更新。此外，SC1 和 RA 通过影响包括 Dnmt3b、Dnmt3l、Tet1、Tet2 和 Tet3 在内的甲基化相关蛋白的表达，影响全局 DNA 甲基化。总之，SC1 主要通过降低磷酸化 Erk1/2 水平和增强 Klf4 的表达来抑制 RA 诱导的 F9 细胞的分化，尽管它也降低 DNA 甲基化，这可能对 ES 细胞分化有额外的影响。
