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Chunk #39 — DISCUSSION

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Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions.
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Our results of directly comparing hESCs with iPSCs suggest that it is true that iPSCs are similar to hESCs. Both functional studies and transcriptome analyses suggest that overall iPSCs derived from somatic cells are largely similar to hESCs. We focused our transcriptome analysis in particular on selected pathways that we and others have suggested may be different between ESCs and iPSCs given the different histories of the ancestor cell that generates a pluripotent population. These include maternal and paternal allele-specific gene expression (imprinting), cell cycle, and senescence, and subtle biases in differentiation due to the source of cells and incomplete reprogramming. Although we did not detect any significant differences, we emphasize that subtle biases are probably best tested in competitive functional assays. Our transplant results suggest that this may be a useful model in which mixed labeled populations can be transplanted in a competitive assay akin to that descried earlier by Jaenisch and coworkers where they showed mouse iPSCs differentiated into functional neurons and glia after transplantation into the developing brain [10].