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Publication : Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells.

First Author  Miyazaki S Year  2004
Journal  Diabetes Volume  53
Issue  4 Pages  1030-7
PubMed ID  15047618 Mgi Jnum  J:103479
Mgi Id  MGI:3609550 Doi  10.2337/diabetes.53.4.1030
Citation  Miyazaki S, et al. (2004) Regulated expression of pdx-1 promotes in vitro differentiation of insulin-producing cells from embryonic stem cells. Diabetes 53(4):1030-7
abstractText  Embryonic stem (ES) cells can differentiate into many cell types. Recent reports have shown that ES cells can differentiate into insulin-producing cells. However, the differentiation is not efficient enough to produce insulin-secreting cells for future therapeutic use. Pdx-1, a homeodomain-containing transcription factor, is a crucial regulator for pancreatic development. We established an ES cell line in which exogenous pdx-1 expression was precisely regulated by the Tet-off system integrated into the ROSA26 locus. Using this cell line, we examined the effect of pdx-1 expression during in vitro differentiation via embryoid body formation. The results showed that pdx-1 expression clearly enhanced the expression of the insulin 2, somatostatin, Kir6.2, glucokinase, neurogenin3, p48, Pax6, PC2, and HNF6 genes in the resulting differentiated cells. Immunohistochemical examination also revealed that insulin was highly produced in most of the differentiated ES cells. Thus, exogenous expression of pdx-1 should provide a promising approach for efficiently producing insulin-secreting cells from human ES cells for future therapeutic use in diabetic patients.
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