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学科主题: 临床医学
题名:
Chromosome microduplication in somatic cells decreases the genetic stability of human reprogrammed somatic cells and results in pluripotent stem cells
作者: Yu, Yang1,2,3; Chang, Liang1; Zhao, Hongcui1; Li, Rong1,2,3; Fan, Yong4; Qiao, Jie1,2,3
刊名: SCIENTIFIC REPORTS
发表日期: 2015-05-12
DOI: 10.1038/srep10114
卷: 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
所属项目编号: 2014CB943203 ; 2011CB944504 ; 31371521 ; 81370766 ; 20110001120008 ; 20120001130008 ; xxjh2015011
项目资助者: 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
WOS记录号: WOS:000354311700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59329
Appears in Collections:北京大学第三临床医学院_生殖医学中心_期刊论文

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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

Recommended Citation:
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.
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