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。
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。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，相关成果文章发表在最新的Genome Research上。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。
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。
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。
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。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
