@article {Parashurama2008474,
	title = {Activin alters the kinetics of endoderm induction in embryonic stem cells cultured on collagen gels},
	journal = {Stem Cells},
	volume = {26},
	number = {2},
	year = {2008},
	note = {cited By 19},
	pages = {474-484},
	abstract = {Embryonic stem cell-derived endoderm is critical for the development of cellular therapies for the treatment of disease such as diabetes, liver cirrhosis, or pulmonary emphysema. Here, we describe a novel approach to induce endoderm from mouse embryonic stem (mES) cells using fibronectin-coated collagen gels. This technique results in a homogeneous endoderm-like cell population, demonstrating endoderm-specific gene and protein expression, which remains committed following in vivo transplantation. In this system, activin, normally an endoderm inducer, caused an 80\% decrease in the Foxa2-positive endoderm fraction, whereas follistatin increased the Foxa2-positive endoderm fraction to 78\%. Our work suggests that activin delays the induction of endoderm through its transient precursors, the epiblast and mesendoderm. Long-term differentiation displays a twofold reduction in hepatic gene expression and threefold reduction in hepatic protein expression of activintreated cells compared with follistatin-treated cells. Moreover, subcutaneous transplantation of activin-treated cells in a syngeneic mouse generated a heterogeneous teratoma-like mass, suggesting that these were a more primitive population. In contrast, follistatin-treated cells resulted in an encapsulated epithelial-like mass, suggesting that these cells remained committed to the endoderm lineage. In conclusion, we demonstrate a novel technique to induce the direct differentiation of endoderm from mES cells without cell sorting. In addition, our work suggests a new role for activin in induction of the precursors to endoderm and a new endoderm-enrichment technique using follistatin. {\textcopyright}AlphaMed Press.},
	doi = {10.1634/stemcells.2007-0303},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-41049100546\&doi=10.1634\%2fstemcells.2007-0303\&partnerID=40\&md5=ede4109f79651bb3ebc0ea9e4d615438},
	author = {Parashurama, N. and Nahmias, Y. and Cho, C.H. and Van Poll, D. and Tilles, A.W. and Berthiaume, F. and Yarmush, M.L.}
}
