陈长征实验室最新《Cell》文章

　　

生物通报道：在4月5日的《Cell》杂志上，来自斯坦福大学医学院微生物和免疫学系的华裔学者陈长征（Chang-Zheng Chen）带领的研究组发表了他们有关microRNA研究的最新成功。这项研究显示，调节性小RNA分子miR-181a是T细胞敏感性和选择性的一种内在调节器。这篇文章的第一作者是陈博士实验室的博士后李奇京（Qi-Jing Li）。

 

已经知道，T细胞对抗原的敏感性在成熟过程中受到内在调节，从而确保免疫力和耐受性的适当发展。但是，这种调节究竟如何完成却还不清楚。

 

在陈长征领导的这项表明，增加成熟T细胞中iR-181a的表达水平能增加对肽抗原的敏感性；而抑制miR-181a在未成熟T细胞中的表达则会降低敏感性并削弱正向和负向选择性。

 

而且，通过miR-181a来定量调节T细胞，能够使成熟T细胞将抑制性肽抗原识别为agonists。这些效果部分通过多磷酸酯酶的下调实现，而磷酸酯酶的萧条导致磷酸化中间产物的水平的增加和T细胞受体信号阈值的降低。

 

更重要的是，较高水平的miR-181a表达与未成熟T细胞中较高的T细胞敏感性相关——这意味着miR-181a是T细胞发育过程中一种内在抗原敏感性“变压器”。

 

陈长征研究室致力于研究受调节性RNA如microRNA和小干扰RNA控制的基因网络以及这些RNA在调节脊椎动物免疫系统发育、功能和致病机理中的作用。（生物通杨遥）

陈长征研究室近年发表的论文精选：

Hyeyoung Min and Chang-Zheng Chen (2006). Methods for analyzing microRNA expression and function during hematopoietic lineage differentiation, Methods in Molecular Biology, 342, 209-227

Chang-Zheng Chen (2005). MicroRNAs as oncogenes and tumor suppressors. New England Journal of Medcine. 353:1768-71.

Chang-Zheng Chen and Harvey F Lodish (2005), MicroRNAs as regulators of mammalian hematopoiesis, Seminar in Immunolgy, 17, 155-165.

David P Bartel, and Chang-Zheng Chen (2004), Micromanagers of gene expression: the potentially widespread influence of microRNAs on mRNA expression and evolution, Nature Review Gentetics, 5, 396-400

Chang-Zheng Chen, Ling Li, Harvey F Lodish and David P Bartel (2004), MicroRNAs Modulate Hematopoietic Lineage Differentiation, Science, 303, 83-6 (Epub 2003 Dec 04)

Chang-Zheng Chen, Ling Li, Min Li, Harvey F Lodish (2003), The EndoglinPositive Sca-1Positive RhodamineLow phenotype defines a near homogeneous population of long–term repopulating hematopoietic stem cells”, Immunity, 19, 525-533

Chang-Zheng Chen, Min Li, David de Graaf, Stefano Monti, Berthold Göttgens, Maria-Jose Sanchez, Eric S Lander, Todd R Golub, Anthony R. Green, Harvey F Lodish (2002), Identification of Endoglin as a novel functional marker that defines long-term repopulating hematopoietic stem cells, Proc. Natl. Acad. Sci. USA. 99, 15468-15473

Robert Shapiro, Ruiz-Gutierrez M, Chang-Zheng Chen (2000), Analysis of the interactions of human ribonuclease inhibitor with angiogenin and ribonuclease A by mutagenesis: importance of inhibitor residues inside versus outside the C-terminal "hot spot". J Mol Biol, 302, 497-519.

Chang-Zheng Chen and Robert Shapiro (1999) Supperadditive and subadditive effects of “Hot Spot” mutation within the interfaces of placental ribonuclease inhibitor with angiogenin and ribonuclease A. Biochemistry, 38, 9273-9285

Chang-Zheng Chen and Robert Shapiro (1997) Site-specific mutagenesis reveals differences in the structural bases for tight binding of ribonuclease inhibitor to angiogenin and ribonuclease A. Proc. Natl. Acad. Sci. USA. 94, 1761-1766

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