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Positive ES cells were selected by using G418, followed by the exposure of the ES cells to retinoic acid. beta-galactosidase-expressing ES cells were aggregated with retinoic acid-treated ES cells in a collagen-coated dish. The ES cell-derived aggregate was cultured for additional 6 days. On day 6 of culture, the insulin-producing cells and glucagon-producing cells were observed in the aggregates. In the present study, insulin- and glucagon-expressing cells were localized in the periphery of aggregates. ES cells were also differentiated into the endodermal cell lineage. ES cells were infected with adenoviral vector carrying retinoid X receptor-specific ligand for gene activation. After retinoid X receptor-specific ligand treatment, the ES cells differentiated into endodermal cell lineages. This is the first report of the differentiation of ES cells into pancreatic cell lineages.# Copyright (c) Microsoft Corporation. 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