Instant neurons: directed somatic cell reprogramming models of central nervous system disorders

Abstract

Nuclear transplantation, cell fusion, and induced pluripotent stem cell studies have revealed a surprising degree of plasticity in mature mammalian cell fates. Somatic cell reprogramming also has been achieved more recently by the directed conversion of nonneuronal somatic cells, such as skin fibroblasts, to neuronal phenotypes. This approach appears particularly applicable to the in vitro modeling of human neurologic disorders. Central nervous system neurons are otherwise difficult to obtain from patients with neurologic disorders; however, nonhuman models may not reflect patient pathology. Somatic cell reprogramming may afford models of nonfamilial "sporadic" neurologic disorders, which are likely caused by multiple interacting genetic and nongenetic factors. Directed somatic cell reprogramming, which does not pass through typical in vivo developmental stages, toward many mature neuronal phenotypes has now been described. This article reviews the field and discusses the potential utilities of such models, such as for the development of personalized medicine strategies.

Keywords: Alzheimer; epigenetic; induced pluripotent neuron; neurodegeneration; reprogramming; somatic; stem cell models.