Noriko Tsubooka1,2, Tomoko Ichisaka3,1, Keisuke Okita1, Kazutoshi Takahashi1, Masato Nakagawa1,2, Shinya Yamanaka3,1,2,4
1Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-material Sciences, Kyoto University, Kyoto 606-8507, Japan
2Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
3CREST and Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
4Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA
Tóm tắt
Pluripotency of embryonic stem (ES) cells is maintained by a network consisting of multiple transcription factors, including Oct3/4, Sox2, Nanog, Klf4 and Sall4. Among these factors, the forced expressions of Oct3/4, Sox2 and Klf4 are sufficient to reprogram fibroblasts into induced pluripotent stem (iPS) cells. The current study analyzed the role of Sall4 during the generation of ES cells and iPS cells. The mouse Sall4 gene was deleted by homologous recombination. Sall4‐null embryos died shortly after implantation, as has been reported. ES‐like cell lines can be established from Sall4‐null blastocysts, albeit with a lower efficiency and a slower time course. The knockdown of Sall4 significantly decreased the efficiency of iPS cell generation from mouse fibroblasts. Furthermore, retroviral transduction of Sall4 significantly increased the efficiency of iPS cell generation in mouse and some human fibroblast lines. These results demonstrated that Sall4 plays positive roles in the generation of pluripotent stem cells from blastocysts and fibroblasts.
