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Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimeticsopen access

Authors
Cho, Seung-JuKim, Keun-TaeJeong, Ho-ChangPark, Ju-ChanKwon, Ok-SeonSong, Yun-HoShin, Joong-GonKang, SeungminKim, WankyuShin, Hyoung DooLee, Mi-OkMoon, Sung-HwanCha, Hyuk-Jin
Issue Date
Nov-2018
Publisher
CELL PRESS
Keywords
BCL-xL; BCL2L1; BH3 mimetics; CTRP; culture adaptation; survival advantage; YM155
Citation
STEM CELL REPORTS, v.11, no.5, pp 1244 - 1256
Pages
13
Journal Title
STEM CELL REPORTS
Volume
11
Number
5
Start Page
1244
End Page
1256
URI
https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69809
DOI
10.1016/j.stemcr.2018.09.002
ISSN
2213-6711
Abstract
The selective survival advantage of culture-adapted human embryonic stem cells (hESCs) is a serious safety concern for their clinical application. With a set of hESCs with various passage numbers, we observed that a subpopulation of hESCs at late passage numbers was highly resistant to various cell death stimuli, such as YM155, a survivin inhibitor. Transcriptome analysis from YM155-sensitive (YM155S) and YM155-resistant (YM155R) hESCs demonstrated that BCL2L1 was highly expressed in YM155R hESCs. By matching the gene signature of YM155R hESCs with the Cancer Therapeutics Response Portal dataset, BH3 mimetics were predicted to selectively ablate these cells. Indeed, short-course treatment with a sub-optimal dose of BH3 mimetics induced the spontaneous death of YM155R, but not YM155S hESCs by disrupting the mitochondrial membrane potential. YM155S hESCs remained pluripotent following BH3 mimetics treatment. Therefore, the use of BH3 mimetics is a promising strategy to specifically eliminate hESCs with a selective survival advantage.
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Moon, Sung-Hwan
대학원 (동물생명공학과.)
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