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Sympk-Oct4 Promotes Self-renewal and Pluripotency of Mouse Embryonic Stem Cells

Review of “Interaction between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation” from STEM CELLS by Stuart P. Atkinson

The ubiquitously expressed scaffold protein Symplekin (Sympk) plays a wide range of reported activities, including RNA polyadenylation [1], transcriptional modulation [2], and the promotion of tumorigenesis [3] to name but a few. Interestingly, previous mass spectrometry analyses by Ding et al. reported the interaction of Sympk with the Oct4 in mouse embryonic stem cells (ESCs) [4], thereby suggesting an additional role for Sympk in the regulation of pluripotency. 

Now, a new STEM CELLS article from the laboratories of Junjiu Huang and Wenbin Ma (SunYat‐sen University, Guangzhou, PR China) confirms that Sympk interacts with Oct4 and suggest that this interaction helps to promote self‐renewal and pluripotency in mouse ESCs and preserve genome integrity [5]. 

Yu et al. discovered that while Sympk overexpression in ESCs significantly increased colony formation, CRISPR/Cas9-mediated deletion promoted cell death and a general decrease in colony formation. Accompanying the increased colony formation, Sympk overexpression also permitted increased ESC proliferation while maintaining both the pluripotent state and genomic stability during long-term passaging. 

Transcriptional analyses also established that Sympk activated proliferation‐related genes and depressed differentiation‐related genes and suggested that Sympk and Oct4 coregulate genes crucial for the maintenance of ESCs. Analysis of the Sympk protein revealed the requirement of a domain of unknown function 3453 (DUF3453) for the previously observed interaction with Oct4, as deletion of this domain prompted a decrease in ESC colony formation in an analogous manner to that observed following Sympk loss.

The authors of this fascinating new study suggest that the Sympk-Oct4 interaction acts to maintain pluripotency and genome stability during long-term in vitro culture, and therefore, may allow for the generation of large amounts of pluripotent stem cells (and their progeny) without a corresponding loss of essential characteristics. Therefore, targeting Sympk in human ESCs or induced pluripotent stem cells may provide a much-needed boost to their regenerative potential.

For more on Sympk, pluripotency, and more, stay tuned to the Stem Cells Portal!


References

  1. Barnard DC, Ryan K, Manley JL, et al., Symplekin and xGLD-2 Are Required for CPEB-Mediated Cytoplasmic Polyadenylation. Cell 2004;119:641-651.
  2. Largeot A, Paggetti J, Broséus J, et al., Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2013;1833:3054-3063.
  3. Buchert M, Papin M, Bonnans C, et al., Symplekin promotes tumorigenicity by up-regulating claudin-2 expression. Proceedings of the National Academy of Sciences 2010;107:2628.
  4. Ding J, Xu H, Faiola F, et al., Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Research 2011;22:155.
  5. Yu J, Lu W, Ge T, et al., Interaction Between Sympk and Oct4 Promotes Mouse Embryonic Stem Cell Proliferation. STEM CELLS 2019;37:743-753.