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
相关论文
共 32 条
  • [21] Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells
    Niwa, H
    Miyazaki, J
    Smith, AG
    [J]. NATURE GENETICS, 2000, 24 (04) : 372 - 376
  • [22] Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3
    Niwa, H
    Burdon, T
    Chambers, I
    Smith, A
    [J]. GENES & DEVELOPMENT, 1998, 12 (13) : 2048 - 2060
  • [23] Functional Splicing Network Reveals Extensive Regulatory Potential of the Core Spliceosomal Machinery
    Papasaikas, Panagiotis
    Ramon Tejedor, J.
    Vigevani, Luisa
    Valcarcel, Juan
    [J]. MOLECULAR CELL, 2015, 57 (01) : 7 - 22
  • [24] Mouse pluripotent stem cells at a glance
    Pauklin, Siim
    Pedersen, Roger A.
    Vallier, Ludovic
    [J]. JOURNAL OF CELL SCIENCE, 2011, 124 (22) : 3727 - 3732
  • [25] BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways
    Qi, XX
    Li, TG
    Hao, J
    Hu, J
    Wang, J
    Simmons, H
    Miura, S
    Mishina, Y
    Zhao, GQ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (16) : 6027 - 6032
  • [26] Regulation of nanog expression by phosphoinositide 3-kinase-dependent signaling in murine embryonic stem cells
    Storm, Mike P.
    Bone, Heather K.
    Beck, Craig G.
    Bourillot, Pierre-Yves
    Schreiber, Valerie
    Damiano, Teresa
    Nelson, Adam
    Savatier, Pierre
    Welham, Melanie J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (09) : 6265 - 6273
  • [27] prpf4 is essential for cell survival and posterior lateral line primordium migration in zebrafish
    Wang, Yixia
    Han, Yanchao
    Xu, Pengfei
    Ding, Shihui
    Li, Guangyuan
    Jin, Hongbin
    Meng, Yaping
    Meng, Anming
    Jia, Shunji
    [J]. JOURNAL OF GENETICS AND GENOMICS, 2018, 45 (08) : 443 - 453
  • [28] Selection of reference genes in mouse embryos and in differentiating human and mouse ES cells
    Willems, Erik
    Mateizel, Ileana
    Kemp, Caroline
    Cauffman, Greet
    Sermon, Karen
    Leyns, Luc
    [J]. INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2006, 50 (07) : 627 - 635
  • [29] MYELOID-LEUKEMIA INHIBITORY FACTOR MAINTAINS THE DEVELOPMENTAL POTENTIAL OF EMBRYONIC STEM-CELLS
    WILLIAMS, RL
    HILTON, DJ
    PEASE, S
    WILLSON, TA
    STEWART, CL
    GEARING, DP
    WAGNER, EF
    METCALF, D
    NICOLA, NA
    GOUGH, NM
    [J]. NATURE, 1988, 336 (6200) : 684 - 687
  • [30] Small molecules that induce cardiomyogenesis in embryonic stem cells
    Wu, X
    Ding, S
    Ding, G
    Gray, NS
    Schultz, PG
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (06) : 1590 - 1591