| Autor: |
Chang WF; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan., Lin TY; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan., Peng M; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan., Chang CC; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan., Xu J; Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, Michigan, USA., Hsieh-Li HM; Department of Life Science, National Taiwan Normal University, Taipei, Taiwan., Liu JL; MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.; School of Life Science and Technology, ShanghaiTech University, Shanghai, China., Sung LY; Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.; Animal Resource Center, National Taiwan University, Taipei, Taiwan. |
| Abstrakt: |
Survival motor neuron (SMN) plays important roles in snRNP assembly and mRNA splicing. Deficiency of SMN causes spinal muscular atrophy (SMA), a leading genetic disease causing childhood mortality. Previous studies have shown that SMN regulates stem cell self-renewal and pluripotency in Drosophila and mouse and is abundantly expressed in mouse embryonic stem cells. However, whether SMN is required for establishment of pluripotency is unclear. In this study, we show that SMN is gradually upregulated in preimplantation mouse embryos and cultured cells undergoing cell reprogramming. Ectopic expression of SMN increased cell reprogramming efficiency, whereas knockdown of SMN impeded induced pluripotent stem cell (iPSC) colony formation. iPSCs could be derived from SMA model mice, but impairment in differentiation capacity may be present. The ectopic overexpression of SMN in iPSCs can upregulate the expression levels of some pluripotent genes and restore the neuronal differentiation capacity of SMA-iPSCs. Taken together, our findings not only demonstrate the functional relevance of SMN in establishment of cell pluripotency but also propose its potential application in facilitating iPSC derivation. |
