Cell：首次成功提取大鼠胚胎干细胞

美国南加州大学一个科研小组12月24日宣布，他们首次成功地从大鼠胚胎中提取干细胞，这将使科学家借助动物模型更方便地对诸多人类顽疾进行研究。

英国科学家马丁·埃文斯早在1981年就成功地从小鼠胚胎中提取出第一个小鼠胚胎干细胞。但大鼠胚胎干细胞的提取尚属首次。

研究负责人、华人科学家应其龙在新闻公报中说，这是干细胞研究领域的一项重大进展，“因为我们知道，与小鼠相比，大鼠在生物学的许多方面与人类更为相近”。应其龙认为，提取大鼠胚胎干细胞研究被证实可行之后，世界许多干细胞实验室的研究方向都将因此而改变。

此前，科研人员尝试提取大鼠胚胎干细胞都因为技术障碍宣告失败。此次，应其龙的科研小组采取了一种特殊的“信号阻断”方法，他们利用特殊的分子抑制大鼠胚胎中3个特定基因发出信号。正常情况下，这3个基因发出的信号是胚胎干细胞分化的“命令”。信号被阻断后，大鼠胚胎干细胞就能够“停下分化的脚步”，保持在原始胚胎阶段。

科研小组认为，能够提取大鼠胚胎干细胞，朝着今后科学家通过基因敲除技术人为地给大鼠胚胎剔除一个或多个基因、培养“定制”大鼠进行疾病研究又向前迈进了一步。

这一成果将发表在定于12月26日出版的《细胞》杂志上。

Cell,26 December 2008 doi:10.1016/j.cell.2008.12.006

Germline Competent Embryonic Stem Cells Derived from Rat Blastocysts

Ping Li1,7,Chang Tong1,Ruty Mehrian-Shai2,3,Li Jia4,Nancy Wu5,Youzhen Yan5,Robert E. Maxson2,5,Eric N. Schulze1,Houyan Song7,Chih-Lin Hsieh2,4,Martin F. Pera1,6andQi-Long Ying1,6,,

1 Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

2 Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

3 Custom Microarray Core Facility, Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

4 Department of Urology, Norris Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

5 USC/Norris Cancer Center Transgenic/Knockout Core Facility, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

6 Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

7 The Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 20032, P.R. China

Rats have important advantages over mice as an experimental system for physiological and pharmacological investigations. The lack of rat embryonic stem (ES) cells has restricted the availability of transgenic technologies to create genetic models in this species. Here, we show that rat ES cells can be efficiently derived, propagated, and genetically manipulated in the presence of small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. These rat ES cells express pluripotency markers and retain the capacity to differentiate into derivatives of all three germ layers. Most importantly, they can produce high rates of chimerism when reintroduced into early stage embryos and can transmit through the germline. Establishment of authentic rat ES cells will make possible sophisticated genetic manipulation to create models for the study of human diseases.