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Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells
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1 Y; F! S0 W% r% [( F/ t3 P! P5 \# pLow reprogramming efficiency and reduced pluripotency have been the two major obstacles in induced pluripotent stem (iPS) cell research. An effective and quick method to assess the pluripotency levels of iPS cells at early stages would significantly increase the success rate of iPS cell generation and promote its applications. We have identified a conserved imprinted region of the mouse genome, the Dlk1-Dio3 region, which was activated in fully pluripotent mouse stem cells but repressed in partially pluripotent cells. The degree of activation of this region was positively correlated with the pluripotency level of stem cells. A mammalian conserved cluster of miRNAs encoded by this region exhibited significant expression differences between full- and partial-pluripotent stem cells. Several miRNAs from this cluster potentially target the PRC2 silencing complex, and may form a feed-forward regulatory loop resulting in the expression of all genes and non-coding RNAs encoded by this region in full-pluripotent stem cells. No other genomic regions were found to exhibit such clear expression changes between cell lines with different pluripotency levels, therefore the Dlk1-Dio3 region may serve as a marker to identify fully pluripotent iPS or ES cells. These findings also provide a step forward toward understanding the operating mechanisms during reprogramming to produce iPS cells, and can potentially promote the application of iPS cells in regenerative medicine and cancer therapy. The putative synergetic effects of several miRNAs also furthered the understanding of the coordinative functions of miRNAs in regulating complex biological processes. ( r* F/ A, e1 c
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周琪- K, D4 |& Z# {( b0 y: D" ?
9 V' Q7 ^. D8 @2 c" d8 D' M) D( w男,37岁,中共党员,博士研究生学历,中国科学院动物研究所研究员、生殖生物学国家重点实验室副主任。4 H3 f. N; }4 ~ x u1 P3 |0 S, T% b
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周琪长期从事克隆技术的研究工作,有多项成果分别发表在Science、Development、Stem- cells、Developmental Biology、Biology of Reproduction、Human Reproduction等世界著名学术刊物上,并成为获得国际转基因研究genOway奖的首位华裔科学家,为我国在动物克隆和胚胎干细胞研究领域取得了突破性进展。, Q( i' D) Y, S
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他先后在中科院和法国国立农业研究中心进行博士后研究。1999年,第一次成功用体细胞克隆出小鼠,被“多莉羊”之父Wilmut博士誉为“该领域迄今为止最重要的成果之一”。 2000年5月,他领导的中法科学家小组合作培育出第一只“胚胎干细胞克隆小鼠”;2000年10月,他用自己发明的“损伤切除术”,成功研制出世界第一头没有利用“多莉”技术生产的体细胞克隆牛“周让娜”,并拥有自主知识产权。2001年8月,他又利用细胞周期同步技术生产出了世界第一头中期体细胞克隆牛“奥运2008”。2002年底,周琪发明了能够精确控制大鼠卵细胞自发活化的专利技术,首次培育出克隆大鼠,获得第三届国际转基因研究genOway奖。
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2002年底,周琪放弃国外优越的科研和生活条件,回国组建起实验室和科研网络,致力于开展克隆和治疗性克隆的研究工作,推动基础研究向临床应用的转化。目前他已建立起小鼠、牛、大鼠和雪貂等多种人类疾病动物模型,建立了70余株治疗性克隆来源的小鼠胚胎干细胞系,建立了人类疾病胚胎干细胞系、人类孤雌干细胞系,改进发明了4项体细胞核移植技术。他在科研方面努力倡导和推动国际合作,并积极对国家的科技政策和管理提出建议,被聘为科技部“海外专家顾问组”顾问。+ A/ c2 {$ c; ?. w* h/ Q- G# W8 C
" X5 V1 U0 L9 v. c 2003年 法中科技促进会生物技术奖# P0 B I" K9 X6 x
2004年 国际转基因研究genOway奖
6 p |' f+ G3 l. O% P% o 2006年 中国科学院Bayer青年科学家奖、第九届中国青年科技奖、入选“百千万人才工程国家级人选” |
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