Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

Autor: Fang Fang, Benjamin Angulo, Renee A. Reijo Pera, Ninuo Xia, Pengbo Zhang, James G. Taylor, Zhengyuan Wang, Rosaria Chiang, Megan Rothstein
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Pluripotent Stem Cells
0301 basic medicine
Neurogenesis
Cellular differentiation
Induced Pluripotent Stem Cells
LIM-Homeodomain Proteins
Bioinformatics
Article
Nestin
03 medical and health sciences
Mesencephalon
hemic and lymphatic diseases
Humans
Medicine
RNA
Messenger

Induced pluripotent stem cell
Cells
Cultured

Embryonic Stem Cells
Oligonucleotide Array Sequence Analysis
Otx Transcription Factors
Multidisciplinary
Sequence Analysis
RNA

business.industry
Dopaminergic Neurons
Gene Expression Profiling
Dopaminergic
nutritional and metabolic diseases
Cell Differentiation
Parkinson Disease
Embryonic stem cell
Gene expression profiling
030104 developmental biology
nervous system
Hepatocyte Nuclear Factor 3-beta
Metabolome
Neuron maturation
Transcriptome
business
Neuroscience
Transcription Factors
Zdroj: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep20270
Popis: 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.
Databáze: OpenAIRE