Differentiation of human pluripotent teratocarcinoma stem cells induced by bone morphogenetic protein-2

Abstract

Pluripotent human teratocarcinoma stem cells culturedin vitro provide a resource for the study of earlyembryonic development in man, as well as a means for discovery of novelfactors controlling cell differentiation and commitment. We previouslyreported that the human teratocarcinoma stem cell line GCT 27X-1 could beinduced to differentiate into an endodermal progenitor cell by treatment withhigh doses of retinoic acid. A search for polypeptide inducers ofdifferentiation in this system has identified bone morphogenetic protein-2(BMP-2) as a potent inducer of differentiation. In cell line GCT 27X-1,treatment with BMP-2 reduces proliferation, induces morphological changessimilar to obtained following treatment with retinoic acid, and causes adecrease in the expression of transcripts for the stem cell markers CD30 andOct-4. Preliminary immunochemical studies indicate that the differentiatedcells produced by BMP-2 are endodermal precursors with a pattern of markerexpression similar to that found in retinoic acid treated cells. Models ofendoderm differentiation in humans will be useful for identifying themolecules which mediate cell interactions in development, and in achievingdirected differentiation of cells for use in transplantation.