Whole-genome gene expression and splicing analysis of midbrain neurons derived from human embryonic stem cells: relevance to Parkinson's disease. Homo sapiens

Directed differentiation of midbrain dopaminergic neurons from human embryonic stem cells (hESCs) has galvanized much interest into their potential application in human Parkinson’s disease (PD). We conducted genome-wide, exon-specific expression analyses at three temporally and phenotypically distinct stages of lineage restriction (pluripotent hESCs, multipotent neural precursor cells and terminally differentiated midbrain dopaminergic neurons). We compare these to expression data generated on the same platform from samples isolated from human fetal brain and from human control postmortem samples isolated from the substantia nigra. This comparison highlights the commonalities and differences between neural cells derived from hESCs and their counterparts in the human brain. This gene expression microarray study was carried out to i) identify changes in gene expression and splicing during neural differentiation to dopaminergic neurons, and ii) determine the maturational state of hESC-derived neuronal samples particularly with regard to genes and pathways relevant to Parkinson's disease. Overall design: 163 samples were analyzed: 5 hESC samples, 4 neural precusor samples, 3 hESC-derived neuronal samples, 94 control fetal brain samples and 57 control adult substantia nigra samples. The control fetal brain samples used in this study originated from GEO Series GSE13344. The 94 CEL files originating from GSE13344 and the 69 CEL files generated within this study were pre-processed together using RMA quantile normalization with GC background correction in Partek’s Genomics Suite v6.6 (Partek Incorporated, USA). In all subsequent analyses, the date of hybridization was included as a covariate. Both gene-level and exon-level analyses were performed. The complete gene-level and exon-level datasets representing: (1) the hESC, neural precursor, hESC-derived neurons, and control adult substantia nigra Samples and (2) the control fetal brain Samples from Series GSE13344 (re-processed using quantile normalization), are linked below as supplementary files.