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

Title
Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimetics
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
Ewha Authors
김완규
SCOPUS Author ID
김완규scopus
Issue Date
2018
Journal Title
STEM CELL REPORTS
ISSN
2213-6711JCR Link
Citation
STEM CELL REPORTS vol. 11, no. 5, pp. 1244 - 1256
Publisher
CELL PRESS
Indexed
SCIE; SCOPUS WOS
Document Type
Article
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.
DOI
10.1016/j.stemcr.2018.09.002
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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