成体干细胞是生物体内少数处于无限增殖、未分化或低分化状态，并具有多种或一种分化潜能的细胞群。干细胞通常存在于一个特殊的微环境中，微环境细胞通过信号分子完成与干细胞的相互作用，进一步调控干细胞的命运，自我更新或分化。
已知许多信号途径参与干细胞的命运决定，但干细胞及其分化子细胞如何差异地响应和解读源于微环境的信号，一直是干细胞生物学研究中悬而未决的基本科学问题之一。
12月10日出版的Cell 杂志，发表了中科院动物研究所陈大华等的一项最新研究成果，研究人员发现干细胞的分化子细胞通过Fused/Smurf复合体主动地拮抗来自微环境的BMP信号，从而在干细胞和分化子细胞之间产生陡峭BMP响应梯度，进而促进干细胞不对称地分裂。
作者还发现Fused和泛素连接酶Smurf形成的复合体，共同调控BMP受体蛋白Tkv的泛素化，进而调节其稳定性。突变体的扫描分析表明，Tkv238位的丝氨酸的磷酸化对Tkv的泛素化和稳定性非常重要，且Fused对Tkv稳定性的调控,依赖该点的磷酸化。
陈大华实验室还与清华大学孟安明实验室合作，以斑马鱼胚胎和人的细胞系为研究系统，进一步发现Fused在脊椎动物中同样具有的拮抗BMP/TGF-?茁信号传导的功能，从而揭示了Fused蛋白所介导的这一调控机制在进化上的保守性，及其在干细胞命运调控和动物发育过程中细胞命运决定的重要作用。（生物谷Bioon.com）
生物谷推荐原文出处：
Cell doi:10.1016/j.cell.2010.11.022
The Fused/Smurf Complex Controls the Fate of Drosophila Germline Stem Cells by Generating a Gradient BMP Response
Laixin Xia, Shunji Jia, Shoujun Huang, Hailong Wang, Yuanxiang Zhu, Yanjun Mu, Lijuan Kan, Wenjing Zheng, Di Wu, Xiaoming Li, Qinmiao Sun, Anming Meng, Dahua Chen
Highlights
CB differentiation involves antagonism of BMP signaling through regulation of Tkv
Fu regulates CB differentiation by antagonizing BMP signal via interaction with Tkv
Fu acts in concert with Smurf to terminate BMP signal by ubiquitinating Tkv in CBs
Fu has a conserved role in antagonizing BMP/TGFβ signals from fly to vertebrate
Summary
In the Drosophila ovary, germline stem cells (GSCs) are maintained primarily by bone morphogenetic protein (BMP) ligands produced by the stromal cells of the niche. This signaling represses GSC differentiation by blocking the transcription of the differentiation factor Bam. Remarkably, bam transcription begins only one cell diameter away from the GSC in the daughter cystoblasts (CBs). How this steep gradient of response to BMP signaling is formed has been unclear. Here, we show that Fused (Fu), a serine/threonine kinase that regulates Hedgehog, functions in concert with the E3 ligase Smurf to regulate ubiquitination and proteolysis of the BMP receptor Thickveins in CBs. This regulation generates a steep gradient of BMP activity between GSCs and CBs, allowing for bam expression on CBs and concomitant differentiation. We observed similar roles for Fu during embryonic development in zebrafish and in human cell culture, implying broad conservation of this mechanism.
