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学科主题临床医学
Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells
Yu, Yang1,2,3; Chang, Liang1; Zhao, Hongcui1; Li, Rong1,2,3; Fan, Yong4; Qiao, Jie1,2,3
刊名SCIENTIFIC REPORTS
2015-05-12
DOI10.1038/srep10114
5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]EPIDERMAL-GROWTH-FACTOR ; NUCLEAR TRANSFER ; HUMAN EMBRYOS ; NEUROTROPHIC FACTOR ; FACTOR-I ; FIBROBLASTS ; GENERATION ; APOPTOSIS ; INSULIN ; MOUSE
英文摘要

Human pluripotent stem cells, including cloned embryonic and induced pluripotent stem cells, offer a limitless cellular source for regenerative medicine. However, their derivation efficiency is limited, and a large proportion of cells are arrested during reprogramming. In the current study, we explored chromosome microdeletion/duplication in arrested and established reprogrammed cells. Our results show that aneuploidy induced by somatic cell nuclear transfer technology is a key factor in the developmental failure of cloned human embryos and primary colonies from implanted cloned blastocysts and that expression patterns of apoptosis-related genes are dynamically altered. Overall, similar to 20%-53% of arrested primary colonies in induced plurpotent stem cells displayed aneuploidy, and upregulation of P53 and Bax occurred in all arrested primary colonies. Interestingly, when somatic cells with pre-existing chromosomal mutations were used as donor cells, no cloned blastocysts were obtained, and additional chromosomal mutations were detected in the resulting iPS cells following long-term culture, which was not observed in the two iPS cell lines with normal karyotypes. In conclusion, aneuploidy induced by the reprogramming process restricts the derivation of pluripotent stem cells, and, more importantly, pre-existing chromosomal mutations enhance the risk of genome instability, which limits the clinical utility of these cells.

语种英语
WOS记录号WOS:000354311700001
项目编号2014CB943203 ; 2011CB944504 ; 31371521 ; 81370766 ; 20110001120008 ; 20120001130008 ; xxjh2015011
资助机构Ministry of Science and Technology of China (973 program) ; National Natural Science Funds for general program ; Ph.D. Programs Foundation of Ministry of Education of Chin ; Beijing Nova Program
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59329
专题北京大学第三临床医学院_生殖医学中心
北京大学第二临床医学院_麻醉科
北京大学第三临床医学院_妇产科
作者单位1.Peking Univ, Hosp 3, Ctr Reprod Med, Dept Obstet & Gynecol, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Assisted Reprod, Beijing 100191, Peoples R China
3.Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing 100191, Peoples R China
4.Guangzhou Med Univ, Affiliated Hosp 3, Key Lab Major Obstetr Dis Guangdong Prov, Guangzhou 510150, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Yu, Yang,Chang, Liang,Zhao, Hongcui,et al. Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells[J]. SCIENTIFIC REPORTS,2015,5.
APA Yu, Yang,Chang, Liang,Zhao, Hongcui,Li, Rong,Fan, Yong,&Qiao, Jie.(2015).Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells.SCIENTIFIC REPORTS,5.
MLA Yu, Yang,et al."Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells".SCIENTIFIC REPORTS 5(2015).
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