Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
J Cell Sci. 2013 Mar 1;126(Pt 5):1093-8. doi: 10.1242/jcs.118273. Epub 2013 Jan 23.
Activation of signal transducer and activator of transcription 3 (Stat3) by leukemia inhibitory factor (LIF) maintains mouse embryonic stem cell (mESC) self-renewal and also facilitates reprogramming to ground state pluripotency. Exactly how LIF/Stat3 signaling exerts these effects, however, remains elusive. We identified gastrulation brain homeobox 2 (Gbx2) as a LIF/Stat3 downstream target that, when overexpressed, allows long-term expansion of undifferentiated mESCs in the absence of LIF/Stat3 signaling. Elevated Gbx2 expression also enhanced reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Moreover, overexpression of Gbx2 was sufficient to reprogram epiblast stem cells to ground state ESCs. Our results reveal a novel function of Gbx2 in mESC reprogramming and LIF/Stat3-mediated self-renewal.
白血病抑制因子（LIF）激活信号转导子和转录激活子 3（Stat3）可维持小鼠胚胎干细胞（mESC）的自我更新，并有助于重编程为原始多能性状态。然而，LIF/Stat3 信号通路如何发挥这些作用仍不清楚。我们发现原肠胚形成脑同源盒 2（Gbx2）是 LIF/Stat3 下游的靶标，当过度表达时，即使在没有 LIF/Stat3 信号的情况下，也允许未分化的 mESC 长期扩增。升高的 Gbx2 表达也增强了小鼠胚胎成纤维细胞向诱导多能干细胞的重编程。此外，Gbx2 的过表达足以将胚外干细胞重编程为原始状态的 ESC。我们的结果揭示了 Gbx2 在 mESC 重编程和 LIF/Stat3 介导的自我更新中的新功能。
