Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

Ninuo Xia; Pengbo Zhang; Fang Fang; Zhengyuan Wang; Megan Rothstein; Benjamin Angulo; Rosaria Chiang; James Taylor; Renee A Reijo Pera

doi:10.1038/srep20270

Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

Sci Rep. 2016 Feb 4:6:20270. doi: 10.1038/srep20270.

Authors

Ninuo Xia¹, Pengbo Zhang¹, Fang Fang¹, Zhengyuan Wang², Megan Rothstein³, Benjamin Angulo¹, Rosaria Chiang¹, James Taylor², Renee A Reijo Pera^{1

3}

Affiliations

¹ Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
² Genomic Medicine Division, Hematology Branch, NHLBI/NIH, MD 20850, USA.
³ Department of Cell Biology and Neurosciences, Montana State University, 207 Montana Hall, Bozeman, MT.

Abstract

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.

MeSH terms

Cell Differentiation
Cells, Cultured
Dopaminergic Neurons / cytology
Dopaminergic Neurons / metabolism*
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism
Gene Expression Profiling
Hepatocyte Nuclear Factor 3-beta / genetics
Hepatocyte Nuclear Factor 3-beta / metabolism
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
LIM-Homeodomain Proteins / genetics
LIM-Homeodomain Proteins / metabolism
Mesencephalon / cytology*
Metabolome
Nestin / genetics
Nestin / metabolism
Neurogenesis
Oligonucleotide Array Sequence Analysis
Otx Transcription Factors / genetics
Otx Transcription Factors / metabolism
Parkinson Disease / metabolism
Parkinson Disease / pathology
Pluripotent Stem Cells / cytology
Pluripotent Stem Cells / metabolism
RNA, Messenger / chemistry
RNA, Messenger / isolation & purification
RNA, Messenger / metabolism
Sequence Analysis, RNA
Transcription Factors / genetics
Transcription Factors / metabolism
Transcriptome*

Substances

FOXA2 protein, human
LIM-Homeodomain Proteins
LMX1A protein, human
Nestin
OTX2 protein, human
Otx Transcription Factors
RNA, Messenger
Transcription Factors
Hepatocyte Nuclear Factor 3-beta