西亚试剂：Germline Competent Embryonic Stem Cells Derived from Rat Bl

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.

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