陈烨光研究组和韩敬东研究组合作在胚胎干细胞发育研究方面取得新的进展（附原文）

细胞海洋

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! w6 v5 Y& e% G. d9 ^  K清华陈烨光研究组和中科院遗传与发育研究所韩敬东研究组合作在胚胎干细胞发育研究方面取得新的进展，相关成果文章Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination发表在最新的《Genome Research》上。
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( _+ |& b: J( I/ z0 \' [' g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。7 n/ K# d  }: b1 ]/ c
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然而，关于细胞外信号如何影响控制胚胎干细胞自我更新转录控制回路的研究一直没有取得太多的进展。为了研究细胞外信号分子对胚胎干细胞，陈烨光、韩敬东研究选择BMP信号来研究胚胎干细胞的分化命运。
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骨形态发生蛋白（Bone Morphogenetic Proteins、BMP）是生长转化因子超家族成员，被认为是目前调控小鼠胚胎干细胞自我更新和分化的重要控制因子。
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研究小组通过全基因组范围上分析BMP信号通路启动子SMAD1/5和SMAD4，发现它们与大量的发育调节因子有很大的关联，如H3K27三甲基，H3K4三甲基标记的调节因子。
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7 ^5 M* H1 T( q1 [Smad敲除试验研究进一步发现，胚胎干细胞自我更新过程中有大量的发育调控因子参与调控过程，在SMAD相关因子研究中鉴定了一些新的调控因子，Dpys12，Ldm6b。这些研究数据表明，SMAD介导的BMP信号调节过程中有大量的调节因子参与。
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" |3 t' C3 [$ ~& O5 _' e' E3楼原文下载 感谢apengforever 提供

细胞海洋

原文检索$ A- M/ Q! r4 I  [- y# x

% i" w4 b& C: m* a3 G( G9 ?" ?Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination
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, L; g' W4 J7 B: S. D) mTeng Fei,Kai Xia,Zhongwei Li,Bing Zhou,Shanshan Zhu,Hua Chen,Jianping Zhang,Zhang Chen,Huasheng Xiao,Jing-Dong J.Han and Ye-Guang Chen
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: ?$ _7 C# t* c$ n2 I+ ~; i) k" xGenome Research
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& s; O$ P/ [" @: KDOI:10.1101/gr.092114.109   j) a5 J  q$ U
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6 d2 w6 r( R% Z# H& Q" I【Abstract】
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Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.
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陈晔光教授、博士生导师- x* [1 D$ h5 L% |3 q+ y
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教育经历:
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1979-1983，就读于江西大学生物系，获生物学学士学位。
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3 ]9 G/ J" F$ f7 }. O1983-1986，就读于江西大学生物系，获动物学硕士学位。$ I5 s* p. m! O2 ?( }* F3 J  Q4 r
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1988-1990，就读于Fordham University，获细胞生物学硕士学位。' [% S+ K7 }5 W# D5 ~
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1991-1996，就读于美国Albert Einstein College of Medicine，获Ph.D.学位2 Y- l$ q9 m8 ~& H' [
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工作经历:
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8 @3 o8 f* B/ k# }. k1996-2000, Post-doctoral Research Associate, Memorial Sloan-Kettering Cancer Center/Howard Hughes Medical Institute. ' A2 r; Z. ~" b  y; ?

) b0 a$ @8 x5 \3 e* z' o  i2000-2002, Assistant Professor, University of California, Riverside.
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5 m8 N8 n- C& a8 t% u2 U7 B7 F2002-至今，清华大学教授。
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研究兴趣、领域5 O2 X4 x! j1 @. U; Y! q% J
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细胞信号转导：利用膜生物学、分子生物学、生物化学、细胞生物学和发育生物学等多学科技术手段研究TGF-β和Wnt信号的调控以及它们在器官发育、干细胞自我更新和分化、肿瘤形成中的作用。. X& w& }$ A% t, @  J

! M! s$ J5 S, Q4 }开设的课程:《细胞生物学》、《细胞信号转导与疾病的发生》、《肿瘤生物学专题讨论》- K, v  o; X4 _. o+ d2 l
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代表性论文：
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　 1.Zuo W, Chen YG# 2009 Specific activation of MAPK by TGF-β receptors in lipid rafts is required for epithelial cell plasticity. Molecular Biology of the Cell, 20:1020-1029.$ U& s1 J) L8 {0 g$ B6 h

! C, R, ?# c* u' \, W8 e. E' P2.Gao X, Wen J, Zhang L, Li X, Ning Y, Meng A, Chen YG#. 2008 Dapper1 is a nucleocytoplasmic shuttling protein that negatively modulates Wnt signaling in the nucleus. Journal of Biological Chemistry, 283:35679-35688.
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3.Zhao X, Nicholls JM, Chen YG# 2008 SARS-CoV nucleocapsid protein interacts with Smad3 and modulates TGF-β signaling. Journal of Biological Chemistry, 283:3272-3280.( p) V; {. p4 k3 G( V( U

* F( X1 J: u. ^& n: C1 ~. t1 U4.Wang Q, Huang Z, Xue H, Jin C, Ju XL, Han JD, Chen YG# 2008 MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4. Blood, 111:588-595.
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5.Lin Z, Gao C, Ning Y, He X, Wu W, Chen YG# 2008 The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/β-catenin signaling. Journal of Biological Chemistry, 283:33053-33058.
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1 @# l' L) _$ c' K2 ?6.Ma J, Wang Q, Fei T, Han JD, Chen YG# 2007 MCP-1 mediates TGF-β-induced angiogenesis by stimulating vascular smooth muscle cell migration. Blood, 109:987-994.3 p: y8 U& E% E' `8 q# m9 a, f% M
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7.Zhang S, Fei T, Zhang L, Zhang R, Chen F, Ning Y, Han Y, Feng XH, Meng A, Chen YG# 2007 Smad7 antagonizes TGF-β signaling in the nucleus by interfering with functional Smad-DNA complex formation. Molecular and Cellular Biology, 27:4488-4499

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