Ed the potential of iPSCs for generating in vitro models of

Ed the potential of iPSCs for generating in vitro models of neurodegenerative maladies, such as, Parkinson's disease, retinal degeneration, amyotrophic* Correspondence: ehashino@iupui.edu 1 Stark Neurosciences Research Institute Full list of author information is available at the end of the articlelateral sclerosis and Rett Syndrome [6-14]. Although these studies are encouraging, little is currently known about the molecular underpinnings of reprogramming and the faithfulness with which iPSCs can recapitulate neuronal differentiation. Although iPSCs of both mouse and human origins appear morphologically indistinguishable from ESCs, several reports have emerged showing variations at the transcriptomic and epigenomic levels [15-22]. In contrast, studies by Guenther et al. [23] and Neumann and Cooper [24], have shown convincingly that the discrepancies between iPSCs and ESCs are not significantly different from variations between ESC lines with divergent genetic backgrounds [23]. Moreover, laboratory-specific factors such as culture conditions and PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/15501003 reprogramming methods may be an underlying cause of these observed?2011 Koehler et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Koehler et al. BMC Neuroscience 2011, 12:82 http://www.biomedcentral.com/1471-2202/12/Page 2 ofdifferences [24]. Variations in teratoma forming ability, hematopoiesis and neuronal differentiation have been observed among mouse and human iPSC lines [25]. Recently, Polo et al. [26], Kim et al. [27] and RRx-001 Marchetto et al. [28], observed that many early-passage mouse iPSC lines maintain a persistent epigenetic signature of the tissue type of origin. Interestingly, when directed to differentiate to hematopoietic or osteogenic cell types, these early-passage cells were biased toward their original cell state, thus leading to low differentiation efficiency [26,27]. At later passages, the iPSCs differentiated more efficiently, which led the researchers to conclude that a period of prolonged cellular proliferation may be a necessary component of the reprogramming process. In light of these findings, it has become clear that newly derived iPSC lines should be thoroughly characterized based on their expression of endogenous pluripotency genes, morphology and differentiation capacity. However, information is lacking whether extensive passaging has effects on the competence of iPSCs to give rise efficiently to a neuronal lineage. The goal of this study was to assess the effects of passaging on genetic stability in iPSCs and their efficiency in giving rise to functional neurons. We also wished to compare the neural differentiation potential of iPSCs with that of ESCs, by performing quantitative evaluation of temporal expression patterns of a battery of genes expressed sequentially during neural development. Due to the reported similarities between iPSC and ESCs, we hypothesized that both cells undergo similar transitions in the expression of key markers of neural differentiation. We found that iPSC lines we generated had variable competence to generate neural cells. We speculated that these discrepancies could stem from the inherent heterogeneity of iPSC cultures prior to differentiation or a residual epigenetic signature from the.