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J. Biol. Chem., Vol. 282, Issue 43, 31703-31712, October 26, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/43/31703    most recent M704287200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bakre, M. M. Articles by Stanton, L. W. Search for Related Content PubMed PubMed Citation Articles by Bakre, M. M. Articles by Stanton, L. W. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Generation of Multipotential Mesendodermal Progenitors from Mouse Embryonic Stem Cells via Sustained Wnt Pathway Activation^*

Manjiri Manohar Bakre¹, Aina Hoi, Jamie Chen Yee Mong, Yvonne Yiling Koh, Kee Yew Wong, and Lawrence W. Stanton

From the Stem Cell and Developmental Biology, Genome Institute of Singapore, 60, Biopolis St. Genome #02-01, Singapore, 138672 and the Department of Biological Sciences, National University of Singapore, Singapore 117543

Pluripotent embryonic stem cells (ESCs) are capable of differentiating into cell types belonging to all three germ layers within the body, which makes them an interesting and intense field of research. Inefficient specific differentiation and contamination with unwanted cell types are the major issues in the use of ESCs in regenerative medicine. Lineage-specific progenitors generated from ESCs could be utilized to circumvent the issue. We demonstrate here that sustained activation of the Wnt pathway (using Wnt3A or an inhibitor of glycogen synthase kinase 3) in multiple mouse and human ESCs results in meso/endoderm-specific differentiation. Using monolayer culture conditions, we have generated multipotential "mesendodermal progenitor clones" (MPC) from mouse ESCs by sustained Wnt pathway activation. MPCs express increased levels of meso/endodermal and mesendodermal markers and exhibit a stable phenotype in culture over a year. The MPCs have enhanced potential to differentiate along endothelial, cardiac, vascular smooth muscle, and skeletal lineages than undifferentiated ESCs. In conclusion, we demonstrate that the Wnt pathway activation can be utilized to generate lineage-specific progenitors from ESCs, which can be further differentiated into desired organ-specific cells.

Received for publication, May 24, 2007 , and in revised form, August 17, 2007.

^* This work was supported by a grant from Agency for Science, Technology and Research, Singapore. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains two supplemental figures and additional text.

This article was selected as a Paper of the Week.

¹ To whom correspondence should be addressed. Tel.: 65-6478-8155; Fax: 65-6478-9005; E-mail: bakre{at}gis.a-star.edu.sg or bmanjiri2002{at}yahoo.com.

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