title: Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells.
abstract: Neural differentiation is an important target of human embryonic stem cells, which provide a source for cell-based therapy, developmental biology, and pharmaceutical research. Previous studies revealed that inhibition of the bone morphogenetic protein is required for neural induction from human embryonic stem cells. On the contrary, the functions of fibroblast growth factors and Activin/Nodal signaling are controversial. Fibroblast growth factor-2 and Activin/Nodal pathways exert divergent influences on human embryonic stem cell concerning the maintenance of both pluripotency and cellular differentiation. We hypothesized that the combination of fibroblast growth factor-2 and Activin A at various concentrations synergistically exerts diverse effects on cell differentiation. To determine the effects of fibroblast growth factor-2 and Activin A on cellular differentiation into neural lineages, we examined the expression of neural differentiation markers in human embryonic stem cells treated with fibroblast growth factor-2 and/or Activin A at various concentrations in a growth factor-defined serum-free medium in short-term culture. In this study, we provide evidence that fibroblast growth factor-2 and Activin A synergistically regulated the initiation of human embryonic stem cell differentiation into neural cell lineages even though human embryonic stem cells autonomously differentiate into neural cell lineages.
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.|Department of Oral Biology & Engineering, Integrated Health Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Mimura
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Suga
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Yujung
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.|Department of Cellular and Molecular Biology, Basic Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kinehara
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Bioengineering, Nagaoka University of Technology, Niigata, 940-2188, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ohnuma
authors.affiliation: Department of Oral Biology & Engineering, Integrated Health Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nikawa
authors.affiliation: Laboratory of Stem Cell Cultures, National Institute of Biomedical Innovation, Health and Nutrition, 7-6-8 Saito Asagi, Ibaraki, Osaka, 567-0085, Japan. mkfurue@gmail.com.
authors.forename: Miho K
authors.initials: MK
authors.lastname: Furue
mesh_terms: D028341:Activins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: C422405:activin A; D016222:Fibroblast Growth Factor 2; D028341:Activins
keywords: Activin A; Cell differentiation; FGF-2; High-throughput assay; Human embryonic stem cells; Neural cell lineage