LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism.

摘要: Murine ES cells can be maintained as a pluripotent, self-renewing population by LIF/STAT3-dependent signaling. The downstream effectors of this pathway have not been previously defined. In report, we identify key target the LIF self-renewal showing that STAT3 directly regulates expression Myc transcription factor. express elevated levels and following withdrawal, mRNA collapse protein becomes phosphorylated on threonine 58 (T58), triggering its GSK3beta dependent degradation. Maintained stable (T58A) renders maintenance pluripotency independent LIF. By contrast, dominant negative form antagonizes promotes differentiation. Transcriptional control suppression T58 phosphorylation are crucial for regulation activity in therefore promoting self-renewal. Together, our results establish mechanism how regulate cell pluripotency.