PRMT5 is required for human embryonic stem cell proliferation but not pluripotency.
PRMT5 is required for human embryonic stem cell proliferation but not pluripotency.
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DOI：
10.1007/s12015-013-9490-z
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发表时间：
2014-04
影响因子：
4.8
通讯作者：
Clark, Amander T.
中科院分区：
文献类型：
--
作者：
Gkountela, Sofia;Li, Ziwei;Chin, Chee Jia;Lee, Serena A.;Clark, Amander T.
关键词：
人类多能干细胞（PSC）是了解调节人类胚胎谱系分化的机制以及再生医学干细胞潜在无限供应的关键体外工具。来自囊胚内细胞团的多能性人类和小鼠胚胎干细胞（ESC）共享相似的转录因子网络以维持多能性和自我更新，但存在相当大的分子差异，反映了小鼠和人类ESC来源的不同环境。在目前的研究中，我们评估了蛋白质精氨酸甲基转移酶5（PRMT5）在人ESC（hESC）自我更新和多能性中的作用，因为它在保护小鼠ESC多能性中起着关键作用。与小鼠不同，我们发现PRMT5在hESC多能性中没有作用。使用微阵列分析，我们发现来自hESC的PRMT5 RNA和蛋白质的显著消耗仅改变了78个基因的表达，其中大多数被抑制。在功能上，我们发现PRMT5的缺失对OCT 4、NANOG或SOX 2的表达没有影响，并且不能防止畸胎瘤的形成。相反，我们表明PRMT5在hESC中的功能是通过调节细胞周期的Gap 1（G1）中的细胞比例和增加G1细胞周期抑制剂P57的表达来调节自我更新状态下的增殖。总之，我们的数据揭示了PRMT5在hESC中的独特作用，并将P57确定为新靶标。
Human pluripotent stem cells (PSCs) are critical in vitro tools for understanding mechanisms that regulate lineage differentiation in the human embryo as well as a potentially unlimited supply of stem cells for regenerative medicine. Pluripotent human and mouse embryonic stem cells (ESCs) derived from the inner cell mass of blastocysts share a similar transcription factor network to maintain pluripotency and self-renewal, yet there are considerable molecular differences reflecting the diverse environments in which mouse and human ESCs are derived. In the current study we evaluated the role of Protein arginine methyltransferase 5 (PRMT5) in human ESC (hESC) self-renewal and pluripotency given its critical role in safeguarding mouse ESC pluripotency. Unlike the mouse, we discovered that PRMT5 has no role in hESC pluripotency. Using microarray analysis we discovered that a significant depletion in PRMT5 RNA and protein from hESCs changed the expression of only 78 genes, with the majority being repressed. Functionally, we discovered that depletion of PRMT5 had no effect on expression of OCT4, NANOG or SOX2, and did not prevent teratoma formation. Instead, we show that PRMT5 functions in hESCs to regulate proliferation in the self-renewing state by regulating the fraction of cells in Gap 1 (G1) of the cell cycle and increasing expression of the G1 cell cycle inhibitor P57. Taken together our data unveils a distinct role for PRMT5 in hESCs and identifies P57 as new target.
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DOI：
10.4161/cc.8.22.10033
发表时间：
2009-11-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Qi J;Yu JY;Shcherbata HR;Mathieu J;Wang AJ;Seal S;Zhou W;Stadler BM;Bourgin D;Wang L;Nelson A;Ware C;Raymond C;Lim LP;Magnus J;Ivanovska I;Diaz R;Ball A;Cleary MA;Ruohola-Baker H
通讯作者：
Ruohola-Baker H
影响因子：
14.9
作者：
Scoumanne A;Zhang J;Chen X
通讯作者：
Chen X
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
56.9
作者：
Thomson, JA;Itskovitz-Eldor, J;Jones, JM
通讯作者：
Jones, JM