title: Phenotype and Stability of Neural Differentiation of Androgenetic Murine ES Cell-Derived Neural Progenitor Cells.
abstract: Uniparental zygotes with two paternal (androgenetic, AG) or two maternal genomes (gynogenetic, GG) cannot develop into viable offsprings but form blastocysts from which pluripotent embryonic stem (ES) cells can be derived. For most organs, it is unclear whether uniparental ES cells can give rise to stably expandable somatic stem cells that can repair injured tissues. Even if previous reports indicated that the capacity of AG ES cells to differentiate in vitro into pan-neural progenitor cells (pNPCs) and into cells expressing neural markers is similar to biparental [normal fertilized (N)] ES cells, their potential for functional neurogenesis is not known. Here we show that murine AG pNPCs give rise to neuron-like cells, which then generate sodium-driven action potentials while maintaining fidelity of imprinted gene expression. Neural engraftment after intracerebral transplantation was achieved only by late (22 days) AG and N pNPCs with in vitro low colony-forming cell (CFC) capacity. However, persisting CFC formation seen, in particular, in early (13 or 16 days) differentiation cultures of N and AG pNPCs correlated with a high incidence of trigerm layer teratomas. As AG ES cells display functional neurogenesis and in vivo stability similar to N ES cells, they represent a unique model system to study the roles of paternal and maternal genomes on neural development and on the development of imprinting-associated brain diseases.
authors: Department of Neurosurgery, University of Würzburg , Würzburg , Germany.
authors: Wanja
authors: W
authors: Wolber
authors: † Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Würzburg , Würzburg , Germany.
authors: Ruhel
authors: R
authors: Ahmad
authors: † Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Würzburg , Würzburg , Germany.
authors: Soon Won
authors: SW
authors: Choi
authors: ‡ Nationwide Children's Research Institute , Columbus, OH , USA.
authors: Sigrid
authors: S
authors: Eckardt
authors: ‡ Nationwide Children's Research Institute , Columbus, OH , USA.
authors: K John
authors: KJ
authors: McLaughlin
authors: † Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Würzburg , Würzburg , Germany.
authors: Jessica
authors: J
authors: Schmitt
authors: § Department of Neurology, University of Würzburg , Würzburg , Germany.
authors: Christian
authors: C
authors: Geis
authors: ¶ Institute for Physiology, University of Würzburg , Würzburg , Germany.
authors: Manfred
authors: M
authors: Heckmann
authors: Department of Neurosurgery, University of Würzburg , Würzburg , Germany.
authors: Anna-Leena
authors: AL
authors: Sirén
authors: † Institute for Medical Radiation and Cell Research (MSZ) in the Center of Experimental and Molecular Medicine (ZEMM), University of Würzburg , Würzburg , Germany.
authors: Albrecht M
authors: AM
authors: Müller
keywords: Brain injury; Electrophysiology; Embryonic stem (ES) cell; Teratoma; Uniparental