Transcriptional comparison of human induced and primary midbrain dopaminergic neurons.

Sci Rep

Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.

Published: February 2016

Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson's disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson's Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740755PMC
http://dx.doi.org/10.1038/srep20270DOI Listing

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