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Characterization of a Human Pluripotent Stem Cell‐derived Model of Neuronal Development Using Multiplexed Targeted Proteomics

Dunkley et al., Proteomics Clin Appl. (2015) - PMID: 25684324

Product(s) used in this publication:  SpikeTides™ - Proteomics Peptide Standards

Abstract:

PURPOSE:

Human pluripotent stem cell (hPSC)-derived cellular models have great potential to enable drug discovery and improve translation of preclinical insights to the clinic. We have developed a hPSC-derived neural precursor cell model for studying early events in human brain development. We present protein-level characterization of this model, using a multiplexed SRM approach, to establish reproducibility and physiological relevance; essential prerequisites for utilization of the neuronal development model in phenotypic screening-based drug discovery.

EXPERIMENTAL DESIGN:

Profiles of 246 proteins across three key stages of in vitro neuron differentiation were analyzed by SRM. Three independently hPSC-derived isogenic neural stem cell (NSC) lines were analyzed across five to nine independent neuronal differentiations.

RESULTS:

One hundred seventy-five proteins were reliably quantified revealing a time-dependent pattern of protein regulation that reflected protein dynamics during in vivo brain development and that was conserved across replicate differentiations and multiple cell lines.

CONCLUSIONS AND CLINICAL RELEVANCE:

SRM-based protein profiling enabled establishment of the reproducibility and physiological relevance of the hPSC-derived neuronal model. Combined with the successful quantification of proteins relevant to neurodevelopmental diseases, this validates the platform for use as a model to enable neuroscience drug discovery.

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

In vitro model; Neuronal development; Phenotypic screen; Pluripotent stem cell; SRM

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