Embryonic stem (ES) cells have been considered as a valuable renewable source of 
materials in regenerative medicine. Recently, we identified the homeoprotein 
EGAM1 both in preimplantation mouse embryos and mouse ES cells. Expression of 
the Egam1 transcript and its encoded protein was detectable in differentiating 
mouse ES cells, while it was almost undetectable in undifferentiated cells. In 
the present study, in order to clarify the effect of forced expression of EGAM1 
on the differentiation of mouse ES cells in vitro, transfectants expressing 
exogenous EGAM1 were generated. Egam1 transfectants promoted differentiation 
into cell types expressing Gata6, Gata4, Afp, or Plat, genes associated with 
emergence of the extra-embryonic endoderm lineages. On the other hand, Egam1 
transfectants inhibited the expression of specific genes for the embryonic 
lineages, including Fgf5 (epiblast) and T (mesoderm), in addition to Cdx2, a 
specific gene for the extra-embryonic trophectoderm lineages. Changes in the 
percentage of cells recognizing by antibodies against specific marker proteins 
closely correlated with the expression patterns of their transcripts. Taken 
together, the results obtained in this study suggested that mouse ES cells 
expressing exogenous EGAM1 preferentially differentiate into extra-embryonic 
primitive endoderm lineages, rather than embryonic lineages or extra-embryonic 
trophectoderm lineages.