Two paternal genomes are compatible with dopaminergic in vitro and in vivo differentiation

Patient derived stem cell-based therapies are considered a future treatment option for Parkinson's disease, a chronic and progressive brain neurodegenerative disorder characterized by depletion of dopaminergic neurons in the basal ganglia. While many aspects of the in vitro and in vivo differentiation potential of uniparental parthenogenetic (PG) and gynogenetic (GG) embryonic stem (ES) cells of several species have been studied, the capacity of androgenetic (AG) ES cells to develop into neuronal subtypes remains unclear. Here, we investigated the potential of murine AG ES cells to undergo dopaminergic differentiation both via directed in vitro differentiation, and in vivo, in ES cell-chimeric E12.5 and E16.5 brains. We show that similar to normal (N; developed from a zygote with maternal and paternal genomes) ES cells, AG cells generated dopaminergic neurons in vitro and in E12.5 and E16.5 chimeric brains following blastocyst injection. Expression of brain-specific imprinted genes was maintained in AG and normal dopaminergic cell cultures. Our results indicate that AG ES cells have dopaminergic differentiation potential in vitro and in vivo. This contrasts with previous reports of limited neural in vivo differentiation of AG cells in later brain development, and suggests that AG ES cells could be therapeutically relevant for future cellular replacement strategies for brain disease.