Gbx2, a LIF/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state.
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.
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.
Chih-I
CI
Tai
Qi-Long
QL
Ying
D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058127:Transcription Factor 3 / Q000378:metabolism*
C513182:Gbx2 protein, mouse; D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D058127:Transcription Factor 3