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EMBRYONIC STEM CELLS

Efficient Derivation of Embryonic Stem Cells by Inhibition of Glycogen Synthase Kinase-3

^aGraduate School of Frontier Biosciences,
^bDepartment of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan;
^cLaboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe, Japan;
^dGenome Information Research Center, Institute for Microbial Diseases, Osaka University, Osaka, Japan; and
^eDepartment of Developmental and Regenerative Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan

Key Words. Embryonic stem cells • Glycogen synthase kinase-3 • Akt • Pluripotency • Stem cells

Correspondence: Toru Nakano, M.D., Ph.D., Department of Pathology, Graduate School of Medicine, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka, Japan 565-0871. Telephone: 81-6-6879-3720; Fax: 81-6-6879-3729; e-mail: tnakano{at}patho.med.osaka-u.ac.jp

Received January 31, 2007; accepted for publication July 9, 2007.
First published online in STEM CELLS EXPRESS   July 19, 2007.



Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocysts. The use of ES cells as a source of differentiated cells holds great promise for cell transplantation therapy. The efficiency of ES cell derivation is affected by genetic variation in mice; that is, some mouse strains, such as C57BL/6, are amenable to ES cell derivation, whereas others, such as BALB/c, are refractory. Developing an efficient method to establish ES cells from strains of various genetic backgrounds should be valuable for derivation of ES cells in various mammalian species, including human. Although it is well-established that various signaling pathways, including phosphoinositide 3-kinase (PI3K)/Akt and Wnt/β-catenin, regulate the maintenance of ES cell pluripotency, little is known about the signaling pathways involved in the derivation of ES cells from ICMs. In this study, we demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3), one of the crucial molecules in the regulation of the Wnt/β-catenin, Hedgehog, and Notch signaling pathways, dramatically augmented ES cell derivation from both C57BL/6 and BALB/c mouse strains. In contrast, Akt signaling activation enhanced the growth of ICM but did not increase the efficiency of ES cell derivation. Our study establishes an efficient means for ES cell derivation by pharmacological inhibition of GSK-3.

Disclosure of potential conflicts of interest is found at the end of this article.

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