胚胎干細(xì)胞(ES cells)來源于植入前胚胎囊胚期的內(nèi)細(xì)胞團(tuán),，具有自我更新和全能性的特點。ES細(xì)胞的自我更新和全能性特性是由細(xì)胞外信號分子和細(xì)胞內(nèi)的關(guān)鍵轉(zhuǎn)錄因子共同調(diào)控的,，如Oct4和Nanog等,。
然而，關(guān)于細(xì)胞外信號如何影響控制胚胎干細(xì)胞自我更新轉(zhuǎn)錄控制回路的研究一直沒有取得太多的進(jìn)展,。清華陳燁光研究組和中科院遺傳與發(fā)育研究所韓敬東研究組合作在胚胎干細(xì)胞發(fā)育研究方面取得新的進(jìn)展,，相關(guān)成果文章發(fā)表在最新的Genome Research上。為了研究細(xì)胞外信號分子對胚胎干細(xì)胞,，陳燁光,、韓敬東研究選擇BMP信號來研究胚胎干細(xì)胞的分化命運。
骨形態(tài)發(fā)生蛋白（Bone Morphogenetic Proteins,、BMP）是生長轉(zhuǎn)化因子超家族成員,，被認(rèn)為是目前調(diào)控小鼠胚胎干細(xì)胞自我更新和分化的重要控制因子。
研究小組通過全基因組范圍上分析BMP信號通路啟動子SMAD1/5和SMAD4,，發(fā)現(xiàn)它們與大量的發(fā)育調(diào)節(jié)因子有很大的關(guān)聯(lián),，如H3K27三甲基，H3K4三甲基標(biāo)記的調(diào)節(jié)因子,。
Smad敲除試驗研究進(jìn)一步發(fā)現(xiàn),，胚胎干細(xì)胞自我更新過程中有大量的發(fā)育調(diào)控因子參與調(diào)控過程，在SMAD相關(guān)因子研究中鑒定了一些新的調(diào)控因子，Dpys12,，Ldm6b,。這些研究數(shù)據(jù)表明，SMAD介導(dǎo)的BMP信號調(diào)節(jié)過程中有大量的調(diào)節(jié)因子參與,。（生物谷Bioon.com）
生物谷推薦原始出處：
Genome Research November 19, 2009, doi:10.1101/gr.092114.109
Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination
Teng Fei1,4, Kai Xia2,4, Zhongwei Li1,5, Bing Zhou2,5, Shanshan Zhu2,5, Hua Chen1, Jianping Zhang1, Zhang Chen2, Huasheng Xiao3, Jing-Dong J. Han2,6 and Ye-Guang Chen1,6
1The State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China;
2CAS Key Laboratory of Molecular Developmental Biology and Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;
3National Engineering Center for Biochip at Shanghai, Zhangjiang Hi-Tech Park, Shanghai 201203, China
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.
