Human Oncostatin M is functionally equivalent to mouse LIF in supporting mouse ES cell pluripotency & germline competency

Maintenance of pluripotency is essential for the use of mouse ES cells in transgenic and knockout stud- ies. A variety of factors have been found to influence ES cell pluripotency, one of which is culture in the presence of Leukemia inhibitory factor (LIF). There are conflicting reports about the ability of Oncostatin M (OSM) to compensate for LIF in ES cell culture. Some have suggested that OSM is not as efficient as LIF in maintenance of ES cell pluripotency, while others have found them equivalent. In the present study, we demonstrate human OSM is able to maintain ES cell pluripotency in a similar manner to mouse LIF, including long-term (10+ passages) maintenance of pluripotency and the ability to differentiate in vitro, the ability to activate STAT3, and germline transmission competency. Our studies suggest that OSM may be an additional factor that plays a role in early embryonic development and that it may be used as an alternative to LIF in mouse ES cell culture. SUMMARY We sought to determine if a closely related cytokine to LIF, Oncostatin M (OSM), could mimic the activ- ity of LIF in the maintenance of embryonic stem (ES) cell pluripotency. We demonstrate that ES cells grown in 10 ng/mL of OSM are able to maintain pluripotency in a manner similar to cells grown in LIF as judged by chimera contribution and germline transmission, expression of markers of pluripotency, and the ability to differentiate in vitro. A slight difference was detected in activation levels of STAT3, a known downstream target of LIF, between ES cells cultured in OSM versus LIF (Figure 4). Since these cells are still able to maintain pluripotency, we hypothesize that this decrease is not significant enough to affect levels of signaling