Abstract：

Human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) have been serving as valuable tools for basic biological research and as promising resources for regeneration therapy. However, one of the current problems is that tumors arise when animal models are transplanted with cell samples containing remaining undifferentiated stem cells.
Here, by comparing the protein expression profiling of ATP-binding cassette (ABC) transporters, we found that two members, ABCB1 and ABCG2, are expressed particularly high in differentiated cells but not in ESC or iPSC. This inspired us to search for cytotoxic substrates for ABCB1/ABCG2 because ABC transporters are of great importance in terms of efflux of various substrates cross plasma membranes. To this aim, we performed viability screening in our natural compound library with cells overexpressing ABCB1 and ABCG2 respectively. Candidate compounds were selected showing specific cytotoxicity in wild type cells but not in ABCB1 or ABCG2 overexpressing cells. The further validation of these compounds was carried out in iPSC. Upon treatment with candidate compounds, iPSC revealed significantly death in dose- and time-dependent manners, while DMSO-treated control or differentiated feeder cells did not. This is the first evidence that specific death of iPSC can be achieved by the compounds specific from ABCB1 and ABCG2 transporters. These candidates may provide an efficient method to diminish undifferentiated ESC and iPSC and reduce the risk of carcinogenesis.

CV：

Ting-Fang Kuo is from Taiwan and received her Dr. of Science degree from Tokyo Institute of Technology in Sep 2011. She is current a post-doctoral research in iCeMS under the supervision of Prof. Uesugi. Her study focuses on how small molecules can be applied to solve biological problems.
Email: tkuo@icems.kyoto-u.ac.jp