PKU is a prevalent type of inherited metabolic disease, caused by the defective phenylalanine metabolism. In most PKU cases, mutations in the PAH gene could be found. Dysfunction of this hepatic enzyme will lead to diverse clinical symptoms due to a failure in converting phenylalanine into tyrosine. Here, we report an integration-free human induced pluripotent stem cell line (NJMUi001-A) generated from peripheral blood mononuclear cells of a PKU patient by using Sendai virus. This iPS cell line has characteristics of pluripotent stem cells and can be used as a useful tool for the investigation of this inherited metabolic disease.
During gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.