To address this issue, transcription factor-mediated reprogramming has been developed to permit the direct induction of desired phenotypes from somatic cells. This technique greatly accelerates the production of desired phenotypes, potentially enabling their use in disorders for which rapid cell replacement is required. Such direct induction of selected neuronal phenotypes was first achieved by Wernig and colleagues (Vierbuchen et al., 2010; Wapinski et al., 2013), and dopaminergic neurons were subsequently induced from somatic cells using a more phenotype-specific set of transcription factors (Hargus et al., 2010; Wernig et al., 2008). These in vitro studies have enabled the production of autologously-derived transplantable neurons in time frames much shorter than achievable using PSCs. More recently, Parmar and colleagues have achieved the in vivo direct induction of striatal neuronal phenotypes from resident glial progenitors (Torper et al., 2015), an approach that may permit the in situ production of desired neuronal phenotypes in a contextually-appropriate fashion. While early in development, this approach promises to potentially negate the need for in vitro production of phenotypes of interest, at least for those diseases in which healthy resident glial progenitors persist and remain amenable to directed phenotypic induction.
