MicroRNAs in the stem cells of the mouse blastocyst

The earliest differentiation event in mammalian embryogenesis is the formation of the inner cell mass (ICM) and the trophoblast compartments of the blastocyst (Theiler, 1989; Kaufman and Bard, 1999). While the ICM gives rise to the embryo proper and to the extraembryonic membranes found in mammals as well as reptiles and birds, the trophoblast contributes exclusively to the placenta, an organ that exists only in eutherian mammals. Pluripotent stem cell lines can be derived from both the ICM and the trophoblast (Evans and Kaufman, 1981; Martin, 1981; Tanaka et al., 1998). Embryonic stem (ES) cells, the derivatives of the ICM, differentiate into all cell types of the embryo proper when injected into recipient blastocysts. Their counterpart, the trophoblastic stem (TS) cells contribute only to the placental lineages of recipient blastocysts. At least some of this in vivo developmental potential can be recapitulated in vitro and the directed differentiation of ES and TS cells into defined cell types is a very active field of study with obvious therapeutic implications. ES cells are almost identical to the so-called embryonic germ (EG) cell lines, which are derived from the primordial germ cells (PGC) of the embryo (Labosky et al., 1994; Stewart et al., 1994). Thus, ES cells are thought to share some characteristics with the germ line stem cells. Indeed, molecules required for the maintenance of the pluripotent ES cell state, such as the transcription factors Nanog and Oct-4, are also expressed in the germ line and its precursors (Niwa et al., 2000; Pesce and Scholer, 2001; Chambers et al., 2003; Mitsui et al., 2003; Kehler et al., 2004).