Germline competent embryonic stem cells derived from rat blastocysts.
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.
Li
Ping
P
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.
Tong
Chang
C
Mehrian-Shai
Ruty
R
Jia
Li
L
Wu
Nancy
N
Yan
Youzhen
Y
Maxson
Robert E
RE
Schulze
Eric N
EN
Song
Houyan
H
Hsieh
Chih-Lin
CL
Pera
Martin F
MF
Ying
Qi-Long
QL
D000818:Animals; D001755:Blastocyst / Q000166:cytology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002678:Chimera; D053595:Embryonic Stem Cells / Q000166:cytology*; D044127:Epigenesis, Genetic; D005260:Female; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors; D038341:Glycogen Synthase Kinases / Q000037:antagonists & inhibitors; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction
D005346:Fibroblast Growth Factors; D038341:Glycogen Synthase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases