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http://dev.biologists.org/content/140/3/675.full
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Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation
$ G- E( |% `1 b$ }Alice E. Chen1,*,§, Malgorzata Borowiak1,‡§, Richard I. Sherwood1,3, Anastasie Kweudjeu1 and Douglas A. Melton1,2,¶
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  R5 p4 U% p. B% e# Y5 R! g& M+ b1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
2 \+ y* y8 h, j/ x1 n7 u2Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
: e' z3 p! G% U' A/ O3 X3Department of Medicine and Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
  c9 a8 |4 ~8 `/ S5 e. |% w+ Author Notes- B4 j1 j# c( ^9 S1 Z
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↵* Present address: Stemgent Inc., 10575 Roselle Street, San Diego, CA 92121, USA4 m; O8 G( J" f+ h: }% I+ Z# b3 l
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↵‡ Present address: Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX 77030, USA
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1 _0 `, @, x; s& u↵§ These authors contributed equally to this work/ C/ }- J* u+ f; r+ |
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↵¶ Author for correspondence (dmelton@harvard.edu)
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  [$ G+ `, f4 [9 v+ c% ?$ m5 Y. mEmbryonic stem (ES) cells hold great promise with respect to their potential to be differentiated into desired cell types. Of interest are organs derived from the definitive endoderm, such as the pancreas and liver, and animal studies have revealed an essential role for Nodal in development of the definitive endoderm. Activin A is a related TGFβ member that acts through many of the same downstream signaling effectors as Nodal and is thought to mimic Nodal activity. Detailed characterization of ES cell-derived endodermal cell types by gene expression analysis in vitro and functional analysis in vivo reveal that, despite their similarity in gene expression, Nodal and Activin-derived endodermal cells exhibit a distinct difference in functional competence following transplantation into the developing mouse embryo. Pdx1-expressing cells arising from the respective endoderm populations exhibit extended differences in their competence to mature into insulin/c-peptide-expressing cells in vivo. Our findings underscore the importance of functional cell-type evaluation during stepwise differentiation of stem cells.

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Functional evaluation of ES cell-derived endodermal populations reveals differences between Nodal and Activin A-guided differentiation