Suppression of PRPF4 regulates pluripotency, proliferation, and differentiation in mouse embryonic stem cells

被引:5
作者
Park, Song [1 ]
Han, Se-Hyeon [7 ,8 ]
Kim, Hyeon-Gyeom [1 ,3 ]
Jeong, Jain [5 ]
Choi, Minjee [1 ,3 ]
Kim, Hee-Yeon [1 ]
Kim, Min-Gi [1 ]
Park, Jin-Kyu [4 ]
Han, Jee Eun [4 ]
Cho, Gil-Jae [4 ]
Kim, Myoung Ok [6 ]
Ryoo, Zae Young [3 ]
Choi, Seong-Kyoon [1 ,2 ]
机构
[1] DGIST, Core Prot Resources Ctr, Daegu, South Korea
[2] DGIST, Div Biotechnol, Daegu, South Korea
[3] Kyungpook Natl Univ, Sch Life Sci, BK21 Plus KNU Creat Biores Grp, 80 Daehakro, Daegu 41566, South Korea
[4] Kyungpook Natl Univ, Coll Vet Med, Daegu, South Korea
[5] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06510 USA
[6] Kyungpook Natl Univ, Dept Anim Sci, Coll Ecol & Environm Sci, Sangju, South Korea
[7] SBS, Dept News Team, Seoul, South Korea
[8] Hanyang Univ, Sch Media Commun, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
differentiation; embryonic stem cells; pluripotency; PRPF4; self-renewal; SELF-RENEWAL; SMALL MOLECULES; EXPRESSION; NANOG; ACTIVATION; GENES; STATE;
D O I
10.1002/cbf.3437
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
Mouse embryonic stem cells (mESCs) are characterized by their self-renewal and pluripotency and are capable of differentiating into all three germ layers. For this reason, mESCs are considered a very important model for stem cell research and clinical applications in regenerative medicine. The pre-mRNA processing factor 4 (PRPF4) gene is known to have a major effect on pre-mRNA splicing and is also known to affect tissue differentiation during development. In this study, we investigated the effects of PRPF4 knockdown on mESCs. First, we allowed mESCs to differentiate naturally and observed a significant decrease in PRPF4 expression during the differentiation process. We then artificially induced the knockdown of PRPF4 in mESCs and observed the changes in the phenotype. When PRPF4 was knocked down, various genes involved in mESC pluripotency showed significantly decreased expression. In addition, mESC proliferation increased abnormally, accompanied by a significant increase in mESC colony size. The formation of mESC embryoid bodies and teratomas was delayed following PRPF4 knockdown. Based on these results, the reduced expression of PRPF4 affects mESC phenotypes and is a key factor in mESC. Significance of the study: Our results indicate that PRPF4 affects the properties of mESCs. Suppression of PRPF4 resulted in a decrease in pluripotency of mESC and promoted proliferation. In addition, suppression of PRPF4 also resulted in decreased apoptosis. Moreover, the inhibition of PRPF4 reduced the ability to differentiate and formation of teratoma in mESC. Our results demonstrated that PRPF4 is a key factor of controlling mESC abilities.
引用
收藏
页码:608 / 617
页数:10
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