Ec Cells

EC cells are the undifferentiated cells derived from teratocarcinomas, malignant multidifferentiated tumors that arise in the testes or ovaries when early mouse embryos are grafted into adult mice (for review see Smith, 2001). These cells can be propogated in culture continuously as undifferentiated cells; however, they retain the ability to differentiate to all three germ layers (ectoderm, mesoderm, and endoderm). Although EC cells are self-renewing and pluripotent in most cases, they lack the ability when reintroduced into the developing embryo to participate in embryogenesis and give rise to a wide variety of tissues. In particular, they are often aneuploid and therefore are not capable of proceeding through meiosis and producing mature sex cells. The most commonly used EC cell lines for the study of RA-dependent differentiation are F9 and P19 cells (Fig. 2).

F9 EC cells resemble the pluripotent stem cells of the inner cell mass of blastocysts. RA induces differentiation of F9 cells along a number of different pathways depending on the culture conditions (Gudas, 1991; Strickland and Mahdavi, 1978; Strickland et al., 1980), mimicking the early commitment events that occur in 3- to 5-day blastocysts when the inner cell mass forms two endodermal layers. Treatment of F9 cells grown in monolayer culture with RA results in differentiation to primitive endoderm, while treatment with both RA and dibutyryl cyclic AMP causes differentiation to parietal endo-derm. These parietal endoderm cells express high levels of plasminogen activator, laminin, and type IV collagen along with very low levels of alkaline phosphatase and lactate dehydrogenase (Strickland and Mahdavi, 1978) typical of parietal endoderm in vivo. On the other hand, treatment of F9 cells grown as aggregates (termed embryoid bodies) in bacterial dishes with

Embryonal carcinoma cells

Mouse early blastocyst implanted in a mouse +

Cells isolated from resultant tumor +

Cultured pluripotent teratocarcinoma cells

P19 cells

F9 cells

Grown Grown as monolayer as aggregates (embryoid bodies)

and cAMP

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