Maintenance of Pluripotency in Human Embryonic Stem Cells Is STAT3 Independent

摘要: The preservation of "stemness" in mouse embryonic stem (mES) cells is maintained through a signal transduction pathway that requires the gp130 receptor, interleukin-6 (IL-6) family cytokines, and Janus Kinase-signal transducer activator (JAK/STAT) pathway. factors signaling pathways regulate human (hES) remain to be elucidated. Here we report STAT3 activation not sufficient block hES cell differentiation when are grown on feeder or they treated with conditioned media from cells. Human ES differentiate presence members IL-6 cytokines including leukemia inhibitory factor (LIF) designer cytokine hyper-IL-6, which complex soluble receptor (IL-6R) greatly enhanced bioactivity. express LIF, IL-6, receptors, as well downstream molecules. Stimulation resulted robust phosphorylation ERK1, ERK2, Akt kinases, transcription factor. Loss pluripotency markers Nanog, Oct-4, TRA-1-60 was observed during gp130-dependent signaling, indicating this insufficient prevent onset differentiation. These data underscore fundamental difference requirements murine versus Furthermore, demonstrate existence an as-yet-unidentified layer acts maintain renewal STAT3-independent manner.