Research on differentiation of endodermal cells from ES cells by introducing genes of transcription factor

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ES cells are proved to be pluripotent and are postulated as good materials for regenerative medicine. Focus of our research is on the differentiation of endodermal cells. As the numerous genes for transcription factor are known to involve in the differentiation, we try to induce the differentiation by introducing the genes in ES cells.Sox17 is on of the crucial genes for development of early stage of endoderm and liver formation. Forced expression of sox17 gene in ES cells results the induction of a set of genes expressed in the endoderm. Moreover dexamethason induce the expression of albumin gene in the sox17-expressing cells. To investigate the in vivo differentiation of sox17-expressing ES cells, we have introduced the EGFP expression unit under SAP (serum amyloid protein) into sox17-expressing ES cells. After one month of injection of these ES cells into liver through splenic vein, EGFP expressing ES cells were found in the liver. Thus sox17-expressing ES cells have suggested to differentiate into mature hepatocyte in vivo.To analyze the effect of sox17 gene in the differentiation of ES cells, we have established the ES cell line in which expression of sox17 gene were regulatable by tetracycline. High density culture in combination with forced expression of sox17 leads to differentiate primitive endoderm cells under regulation of Wnt signals. Using the same strategy to establish the ES cells in which expression of pdx-1 gene, one of the crucial genes for development of pancreas, was regulatable, we can obtain insulin expression cells efficiently.These results will contribute to the understanding of early development of endoderm as well as further progress of regenerative medicine.