GP130 signaling and the control of naïve pluripotency in humans, monkeys, and pigs.

The leukemia inhibitory factor (LIF)/glycoprotein (GP) 130/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 signaling pathway is a hallmark of naïve pluripotency in mice. In this review, we discuss the role of the LIF/GP130/JAK/STAT3 pathway in supporting the naïve-state pluripotency in human, monkey, and pig pluripotent stem cells (PSCs). We highlight the role of LIF/GP130/JAK/STAT3 signaling in reprogramming conventional human and monkey PSCs to naïve-like pluripotency. We analyze published single-cell RNA sequencing datasets of human and monkey embryos and note that the main components of the GP130/JAK/STAT3 pathway are expressed in pluripotent cells at preimplantation stages. We conclude that there is a growing body of evidence supporting the involvement of GP130/JAK/STAT3 in the regulation of naïve pluripotency in non-rodent species including humans, monkeys, and pigs.