HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

OPEN ACCESS ARTICLE

This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2007-0608v1 2007-0608v2 26/4/874    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Shiraki, N. Articles by Kume, S. PubMed PubMed Citation Articles by Shiraki, N. Articles by Kume, S.

EMBRYONIC STEM CELLS

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

Divisions of ^aStem Cell Biology and
^cDevelopmental Genetics, Institute of Molecular Embryology and Genetics,
^b21st Century Center of Excellence, and
^eGlobal Center of Excellence, Kumamoto University, Kumamoto, Japan;
^dDepartment of Reproductive Biology; National Institute for Child Health and Development, Tokyo, Japan

Key Words. Embryonic stem cells • Endoderm induction • Pancreatic differentiation • In vitro differentiation • Growth factors

Correspondence: Shoen Kume, Ph.D., Division of Stem Cell Biology, Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan. Telephone: 81-96-373-6620; Fax: 81-96-373-6807; e-mail: skume{at}kumamoto-u.ac.jp

Received July 30, 2007; accepted for publication January 18, 2008.
First published online in STEM CELLS EXPRESS   January 31, 2008.



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, fibroblast growth factor, or bone morphogenetic protein signals are critical at various steps and that additional short-range signals are required for differentiation into Pdx1-expressing cells. Under selective culture conditions, definitive endoderm (47%) or Pdx1-positive pancreatic progenitors (30%) are yielded at a high efficiency. When transplanted under the kidney capsule, the Pdx1-positive cells further differentiated into all three pancreatic lineages, namely endocrine, exocrine, and duct cells.

Disclosure of potential conflicts of interest is found at the end of this article.

This article has been cited by other articles:

				N. Shiraki, K. Umeda, N. Sakashita, M. Takeya, K. Kume, and S. Kume Differentiation of mouse and human embryonic stem cells into hepatic lineages Genes Cells, July 1, 2008; 13(7): 731 - 746. [Abstract] [Full Text] [PDF]