GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signaling pathway

• Published in: Journal of genetics and genomics 2024-10, Vol.51 (10), p.1055-1065
• Main Authors: Fan, Shasha, Guo, Chuanliang, Yang, Guanheng, Hong, Lei, Li, Hongyu, Ma, Ji, Zhou, Yiye, Fan, Shuyue, Xue, Yan, Zeng, Fanyi
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - genetics; Cell Self Renewal - genetics; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Embryonic stem cell; GPCR; GPR160; JAK1/STAT3 signaling pathway; Janus Kinase 1 - genetics; Janus Kinase 1 - metabolism; Leukemia Inhibitory Factor Receptor alpha Subunit; Mice; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - metabolism; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Signal Transduction - genetics; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism
• ISSN: 1673-8527
• DOI: 10.1016/j.jgg.2024.05.003

G-protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors and regulate various physiological and pathological processes. Despite extensive studies, the roles of GPCRs in mouse embryonic stem cells (mESCs) remain poorly understood. Here, we show that GPR160, a class A member of GPCRs, is dramatically downregulated concurrent with mESC differentiation into embryoid bodies in vitro. Knockdown of Gpr160 leads to downregulation of the expression of pluripotency-associated transcription factors and upregulation of the expression of lineage markers, accompanying with the arrest of the mESC cell-cycle in the G0/G1 phase. RNA-seq analysis shows that GPR160 participates in the JAK/STAT signaling pathway crucial for maintaining ESC stemness, and the knockdown of Gpr160 results in the downregulation of STAT3 phosphorylation level, which in turn is partially rescued by colivelin, a STAT3 activator. Consistent with these observations, GPR160 physically interacts with JAK1, and cooperates with leukemia inhibitory factor receptor (LIFR) and gp130 to activate the STAT3 pathway. In summary, our results suggest that GPR160 regulates mESC self-renewal and pluripotency by interacting with the JAK1–LIFR–gp130 complex to mediate the JAK1/STAT3 signaling pathway.