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上海交通大学973新立项目iPS首席科学家金颖近期在《Stem Cell》再度发表研究性论文Ly-1 Antibody Reactive Clone Is an Important Nucleolar Protein for Control of Self-Renewal and Differentiation in Embryonic Stem Cells。- q# N8 Q4 ^7 g% P3 F5 k: k
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这是金颖教授今年3月在JBC发表研究进展后的又一篇研究性文章，是继研究Oct4与胚胎干细胞的自我更新能力外的又一研究胚胎干细胞自我更新能力的研究成果/ \, Z2 e" T( T" i! o
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+ [% v, f O* n2 U; z6 }5 k; s胚胎干细胞(ES cells)来源于植入前胚胎囊胚期的内细胞团，具有自我更新和全能性的特点。ES细胞的自我更新和全能性特性是由细胞外信号分子和细胞内的关键转录因子共同调控的，如Oct4和Nanog等。
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% T+ p$ x2 A+ B* m' C% c% n! i @在这篇研究性文章中，金颖教授研究小组发现除了Oct4与Nanog以外，Ly-1 Antibody Reactive Clone也是维持胚胎干细胞自我更新和分化能力的重要因子。
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, m1 L9 q% \& ?4 A5 d; p8 r, `5 uLy-1 Antibody Reactive Clone Is an Important Nucleolar Protein for Control of Self-Renewal and Differentiation in Embryonic Stem Cells
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! `3 ~" f; h* S' r; s, JHui Lia,b,c, Beibei Wangb, Acong Yanga,b, Rui Lub, Weicheng Wanga,b,c, Yang Zhoub, Guilai Shib, Sung Won Kwond, Yingming Zhaod, Ying Jina,b,c % b+ Z4 ~! a+ S- C. M
" k2 Y6 ?- f2 d! ~aShanghai Stem Cell Institute, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China5 r- O8 [" X6 s8 t2 [; m) Y
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bKey Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, CAS/Shanghai Jiao Tong University School of Medicine, Shanghai, China4 l2 w7 k) e: Q8 X. R7 j
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cKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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dBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA
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' S$ X/ T- u, U5 {【Abstract】
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/ P7 N2 f( r2 Z, w" h! OEmbryonic stem cells (ESCs) possess the capacity to self-renew and differentiate into all cell types of an organism. It is essential to understand how these properties are controlled for the potential usage of their derivatives in clinical settings and reprogramming of differentiated somatic cells. Although transcriptional factors, such as Oct4, Sox2, and Nanog, have been considered as a part of the core regulatory circuitry, a growing body of evidence suggests that additional factors exist and contribute to the control of ESC self-renewal and differentiation. Here, we report that Ly-1 antibody reactive clone (LYAR), a zinc finger nucleolar protein highly expressed in undifferentiated ESCs, plays a critical role in maintaining ESC identity. Its downregulation significantly reduces the rate of ESC growth and increases their apoptosis. Moreover, reduced expression of LYAR in ESCs impairs their differentiation capacity, failing to rapidly silence pluripotency markers and to activate differentiation genes upon differentiation. Mechanistically, LYAR forms a complex with another nucleolar protein, nucleolin, and prevents its self-cleavage, maintaining a normal steady-state level of nucleolin protein in undifferentiated ESCs. Interestingly, the downregulation of nucleolin is detrimental to the growth of ESCs and increases the rate of apoptosis, similarly to the knockdown of LYAR. Thus, our data emphasize the fact that other genes besides Oct4 and Nanog are uniquely required for ESC self-renewal and differentiation and demonstrate that LYAR functions to control the stability of nucleolin protein, which in turn is essential for maintaining the self-renewal of ESCs. STEM CELLS 2009;27:1244–1254/ l, p) ?3 y6 s
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6 ?' h: j% P! [& Y6 d金颖
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学习经历
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' K$ b! w9 K. _ o, \4 \# J2 Q1978-1983 中国医科大学医学学士% r- E9 E: f$ x( f
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1983-1988 北京协和医科大学/中国医学科学院基础医学研究所理学博士
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& `2 v% C* w! R% Q- ?1988-1994 美国北德克萨斯州大学医学中心博士后
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1994-1999 美国德克萨斯大学西南医学中心博士后' \2 |; a3 s* x+ C5 j0 I
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工作简历
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2000-至今 上海交通大学医学院基础医学院研究员、分子发育生物学研究室主任7 W1 _* B( m$ [9 ?1 ]
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2001-至今 健康科学研究所干细胞研究课题组组长, l! e$ |9 _, Z4 Z) T
4 X; F2 ~% A: E$ t4 R2006-至今 中国科学院干细胞生物学重点实验室主任: m" S3 L( v3 x1 N
% }& [+ ]. t% z, B$ D7 y荣誊(证书,称号,会员)
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International Society for Stem Cell Research会员* n$ H+ l) d, Y" \' s) x0 k) R
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% F2 P# V: N/ c" T- e1. 成功地建立起胚胎干细胞水平研究蛋白质和蛋白质-DNA之间相互作用的技术平台。利用亲和纯化及酵母双杂交等技术筛选出多个与胚胎干细胞全能性因子Oct-3/4相互作用的蛋白质，通过质谱分析发现一个新的蛋白因子Wwp2，Wwp2专一性地与Oct-3/4作用，是Oct-4的E3泛素化连接酶。利用染色质免疫沉淀等方法发现并研究了Oct-3/4的新的下游基因及Oct-3/4对基因表达调控的分子机制。
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2. 建立正常受精及孤雌激活胚胎来源的小鼠ES细胞系，为体外研究ES细胞增殖分化提供了良好的模型；而孤雌干细胞系又有助于基因组印迹及表观遗传在发育中的作用机制的研究。
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3. 建立了人的胚胎干细胞系并实现无滋养层培养和人胚胎干细胞向神经细胞的定向诱导分化。 |
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发表于 2009-7-23 12:51
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