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Scientific article
Open access
English

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

Published inThe AAPS journal, vol. 16, no. 3, p. 400-412
Publication date2014
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
  • 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
Citation (ISO format)
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
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal1550-7416
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208downloads

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