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Fig. 9. Early differentiation events in human ES cell cultures. ES cells undergo spontaneous differentiation in a BMP-dependent fashion to extra-embryonic tissues; the choice of extra-embryonic endoderm or trophoblast (Xu et al., 2002b) depends on environmental factors. Extra-embryonic tissues can produce factors that either drive stem cell renewal or various differentiation pathways. Gremlin produced in feeder cells partially offsets extra-embryonic differentiation locally; addition of noggin to medium completely inhibits this differentiation and allows the formation of neural progenitor through a default mechanism. Lack of extra-embryonic endoderm in noggin-treated cultures results in a loss of signals for stem cell renewal and differentiation into other cell lineages.





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