首页|GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signaling pathway
GPR160 regulates the self-renewal and pluripotency of mouse embryonic stem cells via JAK1/STAT3 signaling pathway
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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 ar-rest 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 co-operates 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.
Department of Histo-Embryology,Genetics and Developmental Biology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China
Shanghai Institute of Medical Genetics,Shanghai Children's Hospital,Shanghai Jiao Tong University,Shanghai 200040,China
NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering,Shanghai 200040,China
School of Pharmacy,Macau University of Science and Technology,Macau 999078,China
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National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaShanghai Key Clinical Specialty ProjectShanghai Top Priority Key Discipline ProjectInnovative Research Team of High-Level Local Universities in ShanghaiMacau Science and Technology Development fund(FDCT)Macau Science and Technology Development fund(FDCT)