Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass . They are capable of undergoing unlimited numbers of symmetrical divisions without differentiation; in addition, they can give rise to differentiated cell types that are derived from all three primary germ layers of the embryo . They can colonize germ lines (resulting in chimeric animals), undergo multilineage differentiation in vitro, and produce a range of well-differentiated progenitors [2, 3], suggesting a potential for ES cells in cell replacement and gene therapy. Apoptosis is critical for many biological events, such as embryonic development, and knowledge of apoptosis of ES cells is important for future use of these cells. Oct-4, a POU homeobox transcription factor, is preferentially expressed and active in ES cells, and expression appears to be required for maintenance of the undifferentiated state of ES cells [4, –6]. Our recent study demonstrated that ES cells did not initiate apoptosis as it does in somatic cells, and this allowed an unusual tolerance to polyploidy . This suggested to us that Oct-4 may be involved in the apoptotic process in ES cells.
Using a tetracycline-inducible murine ES cell line (ZHBtc4) and its parental control line (CGR8), we demonstrated that Oct-4 is an important protector for survival of ES cells from apoptosis induced by etoposide, UV, or heat shock. The Oct-4 effects may be mediated through the Stat3/Survivin pathway, as induced reduction of the expression of Oct-4 was associated with decreased expression of Survivin and phosphorylated Stat3.