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Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell-derived medium spiny neurons.


ABSTRACT: A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE) and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening.

SUBMITTER: Straccia M 

PROVIDER: S-EPMC4571731 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell-derived medium spiny neurons.

Straccia Marco M   Garcia-Diaz Barriga Gerardo G   Sanders Phil P   Bombau Georgina G   Carrere Jordi J   Mairal Pedro Belio PB   Vinh Ngoc-Nga NN   Yung Sun S   Kelly Claire M CM   Svendsen Clive N CN   Kemp Paul J PJ   Arjomand Jamshid J   Schoenfeld Ryan C RC   Alberch Jordi J   Allen Nicholas D ND   Rosser Anne E AE   Canals Josep M JM  

Molecular therapy. Methods & clinical development 20150916


A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific  ...[more]

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