Regulation of in vitro and in vivo differentiation of mouse embryonic stem cells, embryonic germ cells and teratocarcinoma cells by TGFβ family signaling factors

The activity of specific signaling and transcription factors determines the cell fate in normal development and in tumor transformation. The transcriptional profiles of gene-components of different branches of TGFβ family signaling pathways were studied in experimental models of initial stages of three-dimensional in vitro differentiation of embryonic stem cells, embryonic germ cells and teratocarcinoma cells and in teratomas and teratocarcinomas developed after their transplantation into immunodeficient Nude mice. Gene profile analysis of studied cell systems have revealed that expression patterns of ActivinA, Nodal, Lefty1, Lefty2, Tgfβ1, Bmp4, and GDF3 were identical in pluripotent stem cells whereas the mRNAs of all examined genes with the exception of (Inhibin Inhibin βA/ActivinA) were detected in the teratocarcinoma cells. These results indicate that differential activity of signaling pathways of the TGFβ family factors regulates the pluripotent state maintenance and pluripotent stem cell differentiation into the progenitors of three germ layers and extraembryonic structures and that normal expression pattern of TGFβ family factors is rearranged in embryonic teratocarcinoma cells during tumor growth in vitro and in vivo.