Screening of bioactive peptides using an embryonic stem cell-based neurodifferentiation assay

Article Article scientifique Article Screening of bioactive peptides using an embryonic stem cell-based neurodifferentiation assay eng 2014 author Xu Ruodan 737809 author Feyeux Maxime 755543 author Julien Stéphanie 135125 Stéphanie Sgroi author Nemes Csilla 765555 author Albrechtsen Morten author Dinnyés Andras author Krause Karl-Heinz 23022 400-412 10.1208/s12248-014-9578-7 24557747 1550-7416 Differentiation of pluripotent stem cells, PSCs, towards neural lineages has attracted significant attention, given the potential use of such cells for in vitro studies and for regenerative medicine. The present experiments were designed to identify bioactive peptides which direct PSC differentiation towards neural cells. Fifteen peptides were designed based on NCAM, FGFR, and growth factors sequences. The effect of peptides was screened using a mouse embryonic stem cell line expressing luciferase dual reporter construct driven by promoters for neural tubulin and for elongation factor 1. Cell number was estimated by measuring total cellular DNA. We identified five peptides which enhanced activities of both promoters without relevant changes in cell number. We selected the two most potent peptides for further analysis: the NCAM-derived mimetic FGLL and the synthetic NCAM ligand, Plannexin. Both compounds induced phenotypic neuronal differentiation, as evidenced by increased neurite outgrowth. In summary, we used a simple, but sensitive screening approach to identify the neurogenic peptides. These peptides will not only provide new clues concerning pathways of neurogenesis, but they may also be interesting biotechnology tools for in vitro generation of neurons. Animals Cell Differentiation/drug effects Cell Line Drug Evaluation, Preclinical/methods Humans Indicators and Reagents Intercellular Signaling Peptides and Proteins/pharmacology Mice Neural Stem Cells/drug effects Neurites/drug effects/ultrastructure Peptides/pharmacology Dewey 616.07 137 Département de pathologie et immunologie 21F false 38 Radicaux libres et cellules souches embryonnaires 60 The AAPS journal 16 3 57f003a1-5490-4efa-b430-f1c0168edbb0 Article (Published version) Public screening of bioactive.pdf 5422150 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Screening of bioactive peptides using an embryonic stem cell-based neurodifferentiation assay	The AAPS journal			2014	540	213

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Nemes, Csilla