한빛사 논문
- 조회321
Yun-Jeong Kim1, Young-Hyun Go2, Ho-Chang Jeong2, Eun-Ji Kwon1, Seong-Min Kim1, Hyun Sub Cheong3, Wantae Kim4, Hyoung Doo Shin2, Haeseung Lee5 and Hyuk-Jin Cha1
1College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
2Department of Life Sciences, Sogang University, Seoul 04107, Republic of Korea.
3Drug Information Research Institute, College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
4Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Republic of Korea.
5College of Pharmacy, Pusan National University, Busan 46241, Korea.
Corresponding author: Correspondence to Hyuk-Jin Cha.
Abstract
Genetic alterations have been reported for decades in most human embryonic stem cells (hESCs). Survival advantage, a typical trait acquired during long-term in vitro culture, results from the induction of BCL2L1 upon frequent copy number variation (CNV) at locus 20q11.21 and is one of the strongest candidates associated with genetic alterations that occur via escape from mitotic stress. However, the underlying mechanisms for BCL2L1 induction remain unknown. Furthermore, abnormal mitosis and the survival advantage that frequently occur in late passage are associated with the expression of BCL2L1, which is in locus 20q11.21. In this study, we demonstrated that the expression of TPX2, a gene located in 20q11.21, led to BCL2L1 induction and consequent survival traits under mitotic stress in isogenic pairs of hESCs and human induced pluripotent stem cells (iPSCs) with normal and 20q11.21 CNVs. High Aurora A kinase activity by TPX2 stabilized the YAP1 protein to induce YAP1-dependent BCL2L1 expression. A chemical inhibitor of Aurora A kinase and knockdown of YAP/TAZ significantly abrogated the high tolerance to mitotic stress through BCL2L1 suppression. These results suggest that the collective expression of TPX2 and BCL2L1 from CNV at loci 20q11.21 and a consequent increase in YAP1 signaling promote genome instability during long-term in vitro hESC culture.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-01-04)
- 국내 연구진
- 의약학 > 약학
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