title: Functional neuronal cells generated by human parthenogenetic stem cells.
abstract: Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.
authors.affiliation: Institute for Medical Radiation and Cell Research in the Center for Experimental Molecular Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Ruhel
authors.initials: R
authors.lastname: Ahmad
authors.forename: Wanja
authors.initials: W
authors.lastname: Wolber
authors.forename: Sigrid
authors.initials: S
authors.lastname: Eckardt
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.forename: Jessica
authors.initials: J
authors.lastname: Schmitt
authors.forename: Ruslan
authors.initials: R
authors.lastname: Semechkin
authors.forename: Christian
authors.initials: C
authors.lastname: Geis
authors.forename: Manfred
authors.initials: M
authors.lastname: Heckmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: John K
authors.initials: JK
authors.lastname: McLaughlin
authors.forename: Anna-Leena
authors.initials: AL
authors.lastname: Sirén
authors.forename: Albrecht M
authors.initials: AM
authors.lastname: Müller
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D019175:DNA Methylation / Q000235:genetics; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010312:Parthenogenesis