Leukemia inhibitory factor as an anti-apoptotic mitogen for pluripotent mouse embryonic stem cells in a serum-free medium without feeder cells

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Publisher: Springer
Document Type: Article
Length: 368 words

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Byline: Miho Furue (1), Tetsuji Okamoto (2), Yohei Hayashi (3), Hitoshi Okochi (4), Manabu Fujimoto (4), Yasufumi Myoishi (2), Takanori Abe (5), Kiyoshi Ohnuma (3), Gordon H. Sato (6), Makoto Asashima (3,5,7), J. Denry Sato (8) Keywords: ES; mouse embryonic stem cells; serum-free; LIF; nanog; Oct-3/4 Abstract: We have developed a serum-free medium, designated ESF7, in which leukemia inhibitory factor (LIF) clearly stimulated murine embryonic stem (ES) cell proliferation accompanied by increased expression of nanog and Rex-1 and decreased FGF-5 expression. These effects were dependent on the concentration of LIF. The ES cells maintained in ESF7 medium for more than 2 yr retained an undifferentiated phenotype, as manifested by the expression of the transcription factor Oct-3/4, the stem cell marker SSEA-1, and alkaline phosphatase. Withdrawal of LIF from ESF7 medium resulted in ES cell apoptosis. Addition of serum to ESF7 medium promoted ES cell differentiation. Addition of MBP4 promoted ES cell differentiation into simple epithelial-like cells. In contrast, FGF-2 promoted ES cell differentiation into neuronal and glial-like cells. Under serum-free culture conditions, LIF was sufficient to stimulate cell proliferation, it inhibited cell differentiation, and it maintained self-renewal of ES cells. Because this simple serum-free adherent monoculture system supports the long-term propagation of pluripotent ES cells in vitro, it will allow the elucidation of ES cell responses to growth factors under defined conditions. Author Affiliation: (2) Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 734-8553, Hiroshima, Japan (3) Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan (4) Department of Tissue Regeneration, Research Institute, International Medical Center of Japan, 162-8655, Tokyo, Japan (5) Department of Biological Science, Graduate School of Science, The University of Tokyo, Bunkyo-ku, 113-0033, Tokyo, Japan (6) Ministry of Fisheries, Messawa, Eritrea (G.H.S.) (7) International Cooperative Research Project (ICORP)-Japan Science and Technology Agency (JST), The University of Tokyo, 153-8902, Tokyo, Japan (8) Marine Cell Line and Stem Cell Program, Mount Desert Island Biological Laboratory, Salisbury Cove, 04672 (J.D.S.), Maine (1) Department of Biochemistry and Molecular Biology, Kanagawa Dental College, 82 Inaoka-cho, 238-8580, Yokusuka, Japan Article History: Registration Date: 22/03/2007 Received Date: 08/02/2005 Accepted Date: 18/02/2005

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Gale Document Number: GALE|A206220961