Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation
Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation
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DOI：
10.1002/stem.2992
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发表时间：
2019-06
期刊：
影响因子：
5.2
通讯作者：
Jianping Yu;Weisi Lu;Tianyu Ge;Rui Huang;Bohong Chen;Miaoman Ye;Yaofu Bai;Guang Shi;Z. Songyang;Wenbin Ma;Junjiu Huang
中科院分区：
文献类型：
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作者：
Jianping Yu;Weisi Lu;Tianyu Ge;Rui Huang;Bohong Chen;Miaoman Ye;Yaofu Bai;Guang Shi;Z. Songyang;Wenbin Ma;Junjiu Huang
支架蛋白Symplekin（Sympk）参与细胞质RNA聚腺苷酸化、转录调节以及通过紧密连接调节上皮分化和增殖。它在胚胎干细胞（ESC）中高度表达，其作用尚不清楚。在这项研究中，我们发现小鼠胚胎干细胞中的Sympk过表达显著增加了集落形成，而通过CRISPR/Cas9删除Sympk则减少了集落形成。通过畸胎瘤和嵌合小鼠形成评估，Sympk促进ESC生长，其过表达维持ESC多能性。这些细胞在长期传代后保持了基因组稳定性。Sympk中的未知功能域3453（DUF 3453）是其与关键多能因子Oct 4相互作用所必需的，其缺失导致集落形成受损。Sympk激活增殖相关基因并抑制分化相关基因。我们的研究结果表明，Sympk与Oct 4相互作用，促进ESCs的自我更新和多能性，并保持基因组完整性;因此，它对干细胞疗法具有潜在价值。干细胞2019;37：743-753
The scaffold protein Symplekin (Sympk) is involved in cytoplasmic RNA polyadenylation, transcriptional modulation, and the regulation of epithelial differentiation and proliferation via tight junctions. It is highly expressed in embryonic stem cells (ESCs), in which its role remains unknown. In this study, we found Sympk overexpression in mouse ESCs significantly increased colony formation, and Sympk deletion via CRISPR/Cas9 decreased colony formation. Sympk promoted ESC growth and its overexpression sustained ESC pluripotency, as assessed by teratoma and chimeric mouse formation. Genomic stability was preserved in these cells after long‐term passage. The domain of unknown function 3453 (DUF3453) in Sympk was required for its interaction with the key pluripotent factor Oct4, and its depletion led to impaired colony formation. Sympk activated proliferation‐related genes and suppressed differentiation‐related genes. Our results indicate that Sympk interacts with Oct4 to promote self‐renewal and pluripotency in ESCs and preserves genome integrity; accordingly, it has potential value for stem cell therapies. Stem Cells 2019;37:743–753