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。 ! [& j' {% {# Z ( S# N; f6 v, s- Z4 O 8 W6 D3 t6 p1 \$ |1 X! m
! O' N0 E! S& t4 e& ?/ H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+ o% P. B1 ]2 V. i
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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。 $ z; ]; x( f5 Y- m5 I2 m" f. O 6 R. ]5 C" @8 Z' q推荐原文检索： ( x) X$ F+ Z& }" E+ l* `3 c $ R6 J& P+ N4 q/ L) sLy-1 Antibody Reactive Clone Is an Important Nucleolar Protein for Control of Self-Renewal and Differentiation in Embryonic Stem Cells : m; c7 _! |) L6 }
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Hui 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 * K& x$ h# J+ K4 E+ j; r
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aShanghai Stem Cell Institute, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China , w% s3 i3 W9 N+ b4 I6 [4 q L1 C# G1 u: i7 h
bKey Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, CAS/Shanghai Jiao Tong University School of Medicine, Shanghai, China M. G6 j' G9 a2 h 6 N1 F R8 b$ }$ G; d6 N. ] }cKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China . X* H6 d# g7 L+ Y# D, H- [7 J1 B; d: K4 z7 n. H
dBen May Department for Cancer Research, University of Chicago, Chicago, IL, USA ! D# C9 z' M8 g# J2 l! n+ J" [! ^1 a8 {; E6 y+ [: J- X2 u% P
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【Abstract】6 T/ r' s- V& L+ K/ q# V
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Embryonic 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& v- o0 T- R& D3 g' \+ G7 i