Functional neuronal cells generated by human parthenogenetic stem cells

PLoS One. 2012;7(8):e42800. doi: 10.1371/journal.pone.0042800. Epub 2012 Aug 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • DNA Methylation / genetics
  • Dopaminergic Neurons / cytology
  • Dopaminergic Neurons / metabolism
  • Electrophysiological Phenomena / genetics
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting
  • Humans
  • Male
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neuroglia / cytology
  • Neuroglia / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Parthenogenesis*

Grants and funding

This work was supported by the BMBF-funded project 01GN0825 and 01GN1009B, the IZKF Würzburg project D-103, the DFG (SFB-TR3 D2), the EU 7FP project Neurostemcell (#222943) and the Hertie Foundation. RA was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences (GSLS), University of Würzburg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.