期刊
PROTEOMICS CLINICAL APPLICATIONS
卷 9, 期 7-8, 页码 684-694出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/prca.201400150
关键词
In vitro model; Neuronal development; Phenotypic screen; Pluripotent stem cell; SRM
资金
- Roche Postdoctoral Fellowship Program
- Innovative Medicines Initiative Joint Undertaking [115300]
- European Union
- Basel Innovation Hub
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.
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