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Effects of Eight Growth Factors on the Differentiation of Cells Derived from Human Embryonic Stem Cells
Maya Schuldiner, Ofra Yanuka, Joseph Itskovitz-Eldor, Douglas A. Melton and Nissim Benvenisty
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 21 (Oct. 10, 2000), pp. 11307-11312
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/123392
Page Count: 6
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Human embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of in vitro fertilized human blastocysts. We examined the potential of eight growth factors [basic fibroblast growth factor (bFGF), transforming growth factor β 1 (TGF-β 1), activin-A, bone morphogenic protein 4 (BMP-4), hepatocyte growth factor (HGF), epidermal growth factor (EGF), β nerve growth factor (β NGF), and retinoic acid] to direct the differentiation of human ES-derived cells in vitro. We show that human ES cells that have initiated development as aggregates (embryoid bodies) express a receptor for each of these factors, and that their effects are evident by differentiation into cells with different epithelial or mesenchymal morphologies. Differentiation of the cells was assayed by expression of 24 cell-specific molecular markers that cover all embryonic germ layers and 11 different tissues. Each growth factor has a unique effect that may result from directed differentiation and/or cell selection, and we can divide the overall effects of the factors into three categories: growth factors (Activin-A and TGFβ 1) that mainly induce mesodermal cells; factors (retinoic acid, EGF, BMP-4, and bFGF) that activate ectodermal and mesodermal markers; and factors (NGF and HGF) that allow differentiation into the three embryonic germ layers, including endoderm. None of the growth factors directs differentiation exclusively to one cell type. This analysis sets the stage for directing differentiation of human ES cells in culture and indicates that multiple human cell types may be enriched in vitro by specific factors.
Proceedings of the National Academy of Sciences of the United States of America © 2000 National Academy of Sciences