Selective Elimination of Culture-Adapted Human Embryonic Stem Cells with BH3 Mimetics
- 주제(기타) Cell & Tissue Engineering; Cell Biology
- 설명문(일반) [Cho, Seung-Ju; Kim, Keun-Tae; Jeong, Ho-Chang; Shin, Joong-Gon; Shin, Hyoung Doo] Sogang Univ, Dept Life Sci, Seoul 04107, South Korea; [Kang, Seungmin; Kim, Wankyu] Ewha Womans Univ, Ewha Res Ctr Syst Biol, Div Mol & Life Sci, Seoul 03760, South Korea; [Lee, Mi-Ok] KRIBB, Immunotherapy Convergence Res Ctr, Daejeon 34141, South Korea; [Song, Yun-Ho; Moon, Sung-Hwan] Konkuk Univ, Dept Med, Sch Med, 120 Neungdong Ro, Seoul 05029, South Korea; [Park, Ju-Chan; Kwon, Ok-Seon; Cha, Hyuk-Jin] Seoul Natl Univ, Sch Pharm, 1 Gwanak Ro, Seoul 08826, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 CELL PRESS
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156373
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.stemcr.2018.09.002
초록/요약
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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