SC1 inhibits the differentiation of F9 embryonic carcinoma cells induced by retinoic acid

被引:2
作者
Liu, Yingxiang [1 ,2 ]
Ren, Xuexue [1 ,2 ]
Ke, Jie [1 ,2 ]
Zhang, Yan [1 ,2 ]
Wei, Qing [1 ,2 ,3 ]
Shi, Zhaopeng [1 ,2 ]
Ai, Zhiying [1 ,2 ]
Guo, Zekun [1 ,2 ]
机构
[1] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China
[2] Northwest A&F Univ, Minist Agr, Key Lab Anim Biotechnol, Yangling 712100, Shaanxi, Peoples R China
[3] Qinghai Univ, Coll Ecoenvironm Engn, Xining 810016, Qinghai, Peoples R China
基金
中国国家自然科学基金;
关键词
F9 embryonic carcinoma cell; SC1; RA; differentiation; p-Erk1/2; PLURIPOTENT STEM-CELLS; SELF-RENEWAL; DNA METHYLATION; NANOG; PROTEINS; OCT4; EXPRESSION; INDUCTION; SOX2;
D O I
10.1093/abbs/gmy069
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:793 / 799
页数:7
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