| Summary: | 碩士 === 國立中央大學 === 生命科學研究所 === 98 === Embryonic stem (ES) cells have the ability to grow indefinitely while maintaining pluripotency, the ability to differentiate into cells of all three germ layers. They can be used to treat a host of diseases, but there are ethical issues about their sources and problem of the possible immune rejection by the host. In 2006, Takahashi and Yamanaka successfully reprogrammed mouse embryonic fibroblasts to induced pulripotent stem cells (iPS cells) by over-expressing Oct4, Sox2, Klf4 and c-Myc. Although iPS cells open the possibility of autologous stem cell for therapy, it still has some risks, such as insertion mutagenesis and low re-programming efficiency, to be overcome. In 2008, a study showed that some small compounds, such as a histone deacetylase inhibitor called VPA, could increase the reprogramming efficiency. In our study we found that VPA could enhance the Oct4 2k promoter activity both in P19 and C2C12 cells, and it was of interest to define the mechanism. We proposed that VPA might recruit a transcription factors to the Oct4 promoter to activate its activity. We made deletion mutants of the Oct4 promoter and also mutated the hormone receptor-binding site on Oct4 promoter to see whether the VPA activaty will be abrogated. We confirmed that HRE was important in the mechanism of VPA activated the Oct4 promoter. In the future, we want to combine different small compounds to see if the iPS cells reprogramming efficiency will be increased.
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