, 2009) or episomal vectors (Yu et al., 2009), the delivery of excisable lentiviral or transposon vectors (Kaji et al., 2009 and Soldner et al., 2009), the transduction of the reprogramming proteins modified for cellular uptake (Kim et al., 2009), and the direct delivery of synthetic mRNAs modified to escape the endogenous antiviral cell response (Warren et al., 2010). In addition, small molecules can be used to increase the reprogramming efficiency or to replace the activity of one or more of the reprogramming

factors (Huangfu et al., 2008, Li et al., 2009, Lin et al., 2009 and Zhu et al., 2010). However, the generation of iPS cells by using only small molecules has yet to be reported. Thus, the ultimate method in deriving disease-specific iPS cell lines will depend on their downstream use. As a cautionary note, it is important IDO inhibitor Selleckchem SCH727965 to mention that there have been reports indicating differential gene expression and DNA methylation patterns in hES cells and hiPS cells (Chin et al., 2009, Doi et al., 2009 and Lister et al., 2011). However, it is not yet clear what the consequences of this variation are upon stem cell differentiation or functionality of the resulting cell types, if any. From a neurological disease-modeling point of view, it might be more relevant to determine whether hES cells and hiPS cells differ in their ability to reliably generate the differentiated neural cell type(s) of interest. Two recent

studies, including one from our group, compared human ES and hiPS cell lines in terms of their capacity to generate functional motor neurons (Boulting et al., 2011 and Hu et al., 2010). While both studies found variable differentiation efficiency among individual iPS cell lines, Hu and colleagues reported that iPS cell differentiation capacity toward motor neurons was significantly reduced compared to that of hES cells (Hu et al.,

2010), whereas our group found a similar range of differentiation efficiencies when a much larger number of hES and hiPS cell lines were analyzed (Boulting et al., 2011). Our experience suggests that each pluripotent stem cell line, regardless of whether it is an iPS cell or hES cell line, has its own discrete properties that must be taken into consideration when using it for directed very differentiation in disease-modeling studies. Recently, a genomics-based assay has been developed to rapidly characterize the differentiation potential of pluripotent stem cell lines that may aid in predicting the best lines to move forward for neurological applications (Bock et al., 2011). Furthermore, analyses of chromosomal aberrations (Mayshar et al., 2010), subchromosomal copy-number variation (Hussein et al., 2011 and Laurent et al., 2011), protein-coding point mutations (Gore et al., 2011), and DNA methylation profiles (Lister et al., 2011) indicate that hiPS cells can exhibit genetic and epigenetic abnormalities, which can result from the reprogramming process itself or, as with hES cells (Baker et al.