title: Efficient derivation of embryonic stem cells by inhibition of glycogen synthase kinase-3.
abstract: 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/beta-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/beta-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.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Umehara
authors.forename: Tohru
authors.initials: T
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtsuka
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitajima
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D038362:Glycogen Synthase Kinase 3