Guided Differentiation of ES Cells into Pdx1-Expressing Regional Specific Definitive Endoderm

¹ Divisions of Stem Cell Biology; The 21st Century COE, Kumamoto University
² Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan
³ Department of Reproductive Biology, National Institute for Child Health and Development, 2-10-1, Okura, Setagaya, Tokyo, 157-8535, Japan
⁴ Divisions of Stem Cell Biology

^* To whom correspondence should be addressed. E-mail: skume{at}kumamoto-u.ac.jp.

	Abstract

The generation of specific lineages of the definitive endoderm from embryonic stem (ES) cells is an important issue in developmental biology as well as in regenerative medicine. This study demonstrates that ES cells are induced sequentially into regional specific gut endoderm lineages, such as pancreatic, hepatic and other cell lineages, when they are cultured directly on a monolayer of mesoderm-derived supporting cells. A detailed chronological analysis revealed that Activin, FGF or BMP signals are critical at various steps, and that additional short range signals are required for differentiation into Pdx1-expressing cells. Under selective culture conditions, a high efficiency definitive of endoderm (47%) or Pdx1-posititive pancreatic progenitors (30%) are yielded. When transplanted under the kidney capsule, the Pdx1-positive cells further differentiated into all three pancreatic lineages, namely endocrine, exocrine and duct cells.

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