STAT3 is dispensable for maintenance of self-renewal in nonhuman primate embryonic stem cells

The leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway plays an essential role in the maintenance of self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in primate ES cells, including those from humans and monkeys, LIF alone is not sufficient to maintain self-renewal. The precise role of the LIF/gp130/STAT3 pathway for self-renewal in primate ES cells is still unclear. In this study, we found that stimulation of cynomolgus monkey ES cells with LIF or interleukin (IL)-6/soluble IL-6 receptor leads to STAT3 phosphorylation, an effect seen previously in murine ES cells. Concomitant with this notion, nuclear translocalization and transcriptional activation of STAT3 were observed in a LIF-dependent manner. Moreover, the analysis of a dominant interfering mutant, STAT3F, showed that even though the phosphorylation, nuclear translocalization, and transcriptional activation of endogenous STAT3 after LIF stimulation were completely abrogated by overexpressing STAT3F in monkey ES cells, they continued to proliferate in an undifferentiated state, retaining their pluripotency. These results demonstrate that the LIF/gp130/STAT3 pathway functions in cynomolgus monkey ES cells but is not essential for the maintenance of self-renewal. They also suggest that cynomolgus monkey ES cells, unlike murine ES cells, are maintained in an undifferentiated state through LIF/gp130/STAT3-independent signaling.