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

Julien, Stéphanie
Albrechtsen, Morten
Dinnyés, Andras
Published in The AAPS journal. 2014, vol. 16, no. 3, p. 400-412
Abstract 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.
Keywords AnimalsCell Differentiation/drug effectsCell LineDrug Evaluation, Preclinical/methodsHumansIndicators and ReagentsIntercellular Signaling Peptides and Proteins/pharmacologyMiceNeural Stem Cells/drug effectsNeurites/drug effects/ultrastructurePeptides/pharmacology
PMID: 24557747
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Research group Radicaux libres et cellules souches embryonnaires (60)
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XU, Ruodan et al. Screening of bioactive peptides using an embryonic stem cell-based neurodifferentiation assay. In: The AAPS journal, 2014, vol. 16, n° 3, p. 400-412. doi: 10.1208/s12248-014-9578-7 https://archive-ouverte.unige.ch/unige:82444

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Deposited on : 2016-04-07

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