title: Brief exposure to small molecules allows induction of mouse embryonic fibroblasts into neural crest-like precursors.
abstract: In this study, we propose a novel method for inducing neuronal cells by briefly exposing them to small-molecule cocktails in a step-by-step manner. Global gene expression analysis with immunohistochemical staining and calcium flux assays reveal the generation of neurons from mouse embryonic fibroblasts. In addition, time-lapse imaging of neural precursor-specific enhancer expression and global gene expression analyses show that the neurons are generated by passing through a neural crest-like precursor stage. Consistent with these results, the neural crest-like cells are able to differentiate into neural crest lineage cells, such as sympathetic neurons, adipocytes, osteocytes, and smooth muscle cells. Therefore, these results indicate that brief exposure to chemical compounds could expand and induce a substantial multipotent cell population without viral transduction.
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takayama
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Wakabayashi
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kushige
authors.affiliation: Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, Japan.|Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Shinjuku-ku, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.|Department of Plastic and Reconstructive Surgery, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibuya
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Center for Genomic and Regenerative Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Yasuyuki S
authors.initials: YS
authors.lastname: Kida
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D063990:Gene Ontology; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054852:Small Molecule Libraries / Q000494:pharmacology*; D059008:Time-Lapse Imaging / Q000379:methods; D014191:Tranylcypromine / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: C473711:Chir 99021; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D011725:Pyridines; D011743:Pyrimidines; D054852:Small Molecule Libraries; D005576:Colforsin; D014191:Tranylcypromine; D014635:Valproic Acid
keywords: neural crest; peripheral neuron; small molecules