Characterization of a human pluripotent stem cell-derived model of neuronal development using multiplexed targeted proteomics.
Proteomics Clin Appl
; 9(7-8): 684-94, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25684324
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. EXPERIMENTALDESIGN:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Pluripotentes
/
Proteômica
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Proteomics Clin Appl
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Suíça