title: Identification of small molecules that promote human embryonic stem cell self-renewal.
abstract: Human embryonic stem cells (hESCs) and induced pluripotent cells have the potential to provide an unlimited source of tissues for regenerative medicine. For this purpose, development of defined/xeno-free culture systems under feeder-free conditions is essential for the expansion of hESCs. Most defined/xeno-free media for the culture of hESCs contain basic fibroblast growth factor (bFGF). Therefore, bFGF is thought to have an almost essential role for the expansion of hESCs in an undifferentiated state. Here, we report identification of small molecules, some of which were neurotransmitter antagonists (trimipramine and ethopropazine), which promote long-term hESC self-renewal without bFGF in the medium. The hESCs maintained high expression levels of pluripotency markers, had a normal karyotype after 20 passages, and could differentiate into all three germ layers.
authors.affiliation: Department of Embryonic Stem Cell Research, Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Kyoto 606-8507, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kumagai
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suemori
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Eihachiro
authors.initials: E
authors.lastname: Kawase
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008728:Methotrimeprazine / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology*; D010640:Phenothiazines / Q000737:chemistry / Q000494:pharmacology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011398:Promethazine / Q000737:chemistry / Q000494:pharmacology; D054852:Small Molecule Libraries; D014291:Trimeprazine / Q000737:chemistry / Q000494:pharmacology; D014299:Trimipramine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D050814:Octamer Transcription Factor-3; D009930:Organic Chemicals; C494173:POU5F1 protein, human; D010640:Phenothiazines; D054852:Small Molecule Libraries; D049452:Green Fluorescent Proteins; D014299:Trimipramine; D014291:Trimeprazine; C084820:profenamine; D008728:Methotrimeprazine; D011398:Promethazine