CONTROLLED CONVERSION OF AN IMMORTALIZED MESODERMAL PROGENITOR-CELL TOWARDS OSTEOGENIC, CHONDROGENIC, OR ADIPOGENIC PATHWAYS

The teratocarcinoma-derived C1 clone behaves as a mesodermal tripotent ial progenitor cell whose choice of fate, either osteoblast, chondrobl ast, or adipoblast, is strictly dependent on the spatial organization of the cells and the nature of the induction. In the absence of cell c ontact before the addition of inducers, the C1 cells maintain a stable undifferentiated phenotype while expressing potential regulators of e mbryonic mesodermal stem cell fate such a M-twist and Idl. Upon establ ishment of cell contacts before the induction of differentiation, the early genes characteristic of the three fates become expressed. In the presence of beta glycerophosphate and ascorbate, provided the cells h ave formed aggregates, 95% of the C1 cells mineralize with a kinetics of gene expression close to that of osteoblasts (Pollard, A., D. Lambl in, P. J. Marie, M. H. Buc, and O. Kellermann. 1993. J. Cell Sci. 106: 503-512). With 10(-6)M dexamethasone: 80% of the same aggregates diffe rentiate into foci of chondroblast-like cells. The kinetics of express ion of the genes encoding type II, IX, X, and XI collagens, aggrecan a nd link protein during the conversion towards cartilage hypertrophy re sembles that accompanying in vivo chondrogenesis. The synergistic acti on of dexamethasone and insulin convert most confluent C1 cells into f unctional adipocytes and induce a pattern of gene expression close to that reported for adipoblast cell lines. The C1 clone with its capacit y to differentiate along three alternative pathways with high frequenc y, therefore appears as a valid in vitro model for deciphering the mol ecular basis of mesoblast ontogeny.