DIFFERENTIATION OF SERUM-FREE MOUSE EMBRYO CELLS INTO ASTROCYTES IS ACCOMPANIED BY INDUCTION OF GLUTAMINE-SYNTHETASE ACTIVITY

Serum-free mouse embryo (SFME) cells derived in a defined serum-free m edium have been cultured for more than 200 generations and display pro perties of neural progenitor cells. SFME cells express the neuroepithe lial stem cell marker nestin in defined serum-free medium, Exposure of SFME cells to transforming growth factor beta (TGF-beta) or serum dec reases nestin expression and induces the astrocyte marker glial fibril lary acidic protein, suggesting that SFME cells differentiate into ast rocytes upon exposure to TGF-beta or serum, We examined the expression by SFME cells of the functional central nervous system (CNS) astrocyt e marker glutamine synthetase (GS), GS activity is induced in SFME cel ls upon exposure to TGF-beta or serum, The induction of GS activity wa s dose- and time-dependent and was reversible, Retinoic acid, hydrocor tisone, and dibutyryl cyclic AMP also induced GS expression, The induc tion of GS activity was accompanied by an increase in the level of GS mRNA and protein, This work provides further evidence that SFME cells represent neural progenitor cells which differentiate into functional astrocytes upon exposure to TGF-beta or serum. (C) 1995 Wiley-Liss, In c.