title: The majority of early primordial germ cells acquire pluripotency by AKT activation.
abstract: Primordial germ cells (PGCs) are undifferentiated germ cells in embryos, the fate of which is to become gametes; however, mouse PGCs can easily be reprogrammed into pluripotent embryonic germ cells (EGCs) in culture in the presence of particular extracellular factors, such as combinations of Steel factor (KITL), LIF and bFGF (FGF2). Early PGCs form EGCs more readily than do later PGCs, and PGCs lose the ability to form EGCs by embryonic day (E) 15.5. Here, we examined the effects of activation of the serine/threonine kinase AKT in PGCs during EGC formation; notably, AKT activation, in combination with LIF and bFGF, enhanced EGC formation and caused ∼60% of E10.5 PGCs to become EGCs. The results indicate that the majority of PGCs at E10.5 could acquire pluripotency with an activated AKT signaling pathway. Importantly, AKT activation did not fully substitute for bFGF and LIF, and AKT activation without both LIF and bFGF did not result in EGC formation. These findings indicate that AKT signal enhances and/or collaborates with signaling pathways of bFGF and of LIF in PGCs for the acquisition of pluripotency.
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan CREST, JST, Kawaguchi, Saitama 332-0012, Japan ymatsui@idac.tohoku.ac.jp.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Takehara
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan CREST, JST, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tokitake
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Obara
authors.affiliation: Frontier Research Institute of Interdisciplinary Sciences (FRIS), Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Morita-Fujimura
authors.affiliation: School of Science, Kitasato University, Sagamihara, Kanagawa 252-0373, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kimura
authors.affiliation: CREST, JST, Kawaguchi, Saitama 332-0012, Japan Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000502:physiology*; D002678:Chimera / Q000196:embryology; D047108:Embryonic Development / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005838:Genotype; D005854:Germ Cells / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D019089:Stem Cell Factor / Q000378:metabolism
chemical_list: D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D009842:Oligopeptides; D019089:Stem Cell Factor; C588228:lysyl-arginyl-threonyl-glycyl-glutaminyl-tyrosyl-lysyl-leucyl-cysteine; D016222:Fibroblast Growth Factor 2; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; EGCs; LIF; PGCs; bFGF