SC1 inhibits the differentiation of F9 embryonic carcinoma cells induced by retinoic acid.
SC1 inhibits the differentiation of F9 embryonic carcinoma cells induced by retinoic acid.
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SC1抑制视黄酸诱导的F9胚胎癌细胞的分化。
DOI：
10.1093/abbs/gmy069
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
郭泽坤
中科院分区：
文献类型：
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作者：
郭泽坤
自我更新能力是胚胎干细胞最重要的特性之一。Pluripotin（SC 1）是一种高活性、低毒性的小分子，可促进小鼠ES细胞的自我更新。SC 1能显著改变维甲酸（RA）诱导的F9胚胎癌细胞（F9细胞）的形态。然而，从长远来看，RA和SC 1共同导致细胞凋亡。当在RA诱导的F9细胞分化18-24小时后加入时，SC 1暂时激活Nanog和Oct 4。当同时加入SC 1和RA时，Nanog和Oct 4均下调。另一方面，Klf 4在加入SC 1 6 - 24 h之间持续活化。磷酸化Erk 1/2蛋白水平从6小时至24小时降低，而非磷酸化Erk 1蛋白水平保持不变。较高浓度的SC 1通过增强对F9细胞Erk 1/2蛋白磷酸化的抑制作用促进细胞自我更新。此外，SC 1和RA通过影响甲基化相关蛋白的表达来影响整体DNA甲基化，包括Dnmt 3b，Dnmt 3l，Tet 1，Tet 2和Tet 3。总之，SC 1抑制RA诱导的F9细胞的分化，主要是通过降低磷酸化的Erk 1/2的水平和提高Klf 4的表达，虽然它也降低DNA甲基化，这可能有一个额外的影响ES细胞分化。
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.