Reprogramming relies on the expression of certain TFs in order for the original somatic tissue to acquire pluripotency. However, directing somatic cells to a pluripotent state could alter the epigenetic character of the original donor cells (Hochedlinger & Plath, 2009; Lunyak & Rosenfeld, 2008; Meissner, 2010; Pasque, Jullien, Miyamoto, Halley-Stott, & Gurdon, 2011; Spivakov & Fisher, 2007). Thus, the environmental effects of alcohol exposure in alcoholic individuals are not likely to be maintained during reprogramming (i.e. epigenetics) (Table 1). Interestingly, a recent study reported that iN cells but not neurons derived from iPS cells maintained age related epigenetic marks (Mertens, Paquola, et al., 2015). The iN cells are generated by ectopic expression of proneuronal differentiation specific TFs (Pang et al., 2011; Vierbuchen et al., 2010) that allows generation of subtype specific human neuronal cells including excitatory (Zhang et al., 2013), inhibitory (Yang et al., 2017) and dopaminergic (Fantuzzo et al., 2017) flavors. Thus, iN cell models may provide a viable model system that potentially maintains the epigenetic modifications contributing to the disease.
