Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation. (9th March 2019)

• Record Type: Journal Article
• Authors: Yu, Jianping; Lu, Weisi; Ge, Tianyu; Huang, Rui; Chen, Bohong; Ye, Miaoman; Bai, Yaofu; Shi, Guang; Songyang, Zhou; Ma, Wenbin; Huang, Junjiu
• Is Part Of: Stem cells. Volume 37:Number 6(2019)
• Page Start: 743
• Page End: 753
• Publication Date: 2019-03-09
• Subjects: Symplekin -- Oct4 -- Embryonic stem cells -- Proliferation -- Pluripotency -- Genomic stability; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2992
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : 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 : Abstract : Large expansion of embryonic stem cells sustaining stemness and genomic stability is a bottleneck before meeting the demands of clinical transplantation. Here, we found a scaffold protein Symplekin is enriched in mouse embryonic stem cells. Its overexpression enhanced cell proliferation, maintained pluripotency and genomic stability during long-term culture both in vitro and in vivo, whereas its deficiency impaired mouse embryonic stem cells self-renewability. Mechanistically, the DUF3453 domain of Symplekin was sufficient for its binding with the key pluripotency factor Oct4 and essential for mouse embryonic stem cell colony formation. Finally, Symplekin could promote genome-wide proliferative genes and inhibit differentiation genes. Thus, Symplekin is a potential candidate for optimizing embryonic stem cell culture and expansion.