title: Transcriptional comparison of human induced and primary midbrain dopaminergic neurons.
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.
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors: Ninuo
authors: N
authors: Xia
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors: Pengbo
authors: P
authors: Zhang
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors: Fang
authors: F
authors: Fang
authors: Genomic Medicine Division, Hematology Branch, NHLBI/NIH, MD 20850, USA.
authors: Zhengyuan
authors: Z
authors: Wang
authors: Department of Cell Biology and Neurosciences, Montana State University, 207 Montana Hall, Bozeman, MT.
authors: Megan
authors: M
authors: Rothstein
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors: Benjamin
authors: B
authors: Angulo
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.
authors: Rosaria
authors: R
authors: Chiang
authors: Genomic Medicine Division, Hematology Branch, NHLBI/NIH, MD 20850, USA.
authors: James
authors: J
authors: Taylor
authors: Department of Genetics; Department of Obstetrics and Gynecology; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, CA, USA.|Department of Cell Biology and Neurosciences, Montana State University, 207 Montana Hall, Bozeman, MT.
authors: Renee A
authors: RA
authors: Reijo Pera
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology*; D055442:Metabolome; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D020411:Oligonucleotide Array Sequence Analysis; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: C496502:FOXA2 protein, human; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D064231:Nestin; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta