Efficient Derivation Of Embryonic Stem Cells By Inhibition Of Glycogen Synthase Kinase-3

¹ Graduate School of Frontier Biosciences
² Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, Japan 565-0871
³ Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan
⁴ Gemone Information Research Center, Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan 565-0871
⁵ Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Developmental and Regenerative Medicine, Graduate School of Medicine, Kobe University, 7-5-1 Kusunokicho, Chuo-ku, Kobe 650-0017, Japan
⁶ Graduate School of Frontier Biosciences; Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, Japan 565-0871

^* To whom correspondence should be addressed. E-mail: tnakano{at}patho.med.osaka-u.ac.jp.

	Abstract

Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocysts. Usage 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, i.e., 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/-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/-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.

This article has been cited by other articles:

				T. Nakamura, K. Inoue, S. Ogawa, H. Umehara, N. Ogonuki, H. Miki, T. Kimura, A. Ogura, and T. Nakano Effects of Akt signaling on nuclear reprogramming Genes Cells, December 1, 2008; 13(12): 1269 - 1277. [Abstract] [Full Text] [PDF]

				T. Kimura, M. Tomooka, N. Yamano, K. Murayama, S. Matoba, H. Umehara, Y. Kanai, and T. Nakano AKT signaling promotes derivation of embryonic germ cells from primordial germ cells Development, March 1, 2008; 135(5): 869 - 879. [Abstract] [Full Text] [PDF]