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 ce...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 formaintaining 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.展开更多
To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane domain1.By playing crucial roles in regulation of various physio...To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane domain1.By playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and cancer.To initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.展开更多
基金This work was funded by grants from the National Key Research and Development Program of China(2019YFA0801402)the National Natural Science Foundation of China(82271890)+3 种基金the Shanghai Key Clinical Specialty Project(shslczdzk05705)the Shanghai Top Priority Key Discipline Project(2017zz02019)Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212200)the Macao Science and Technology Development fund(FDCT)(0092/2022/A2 and 003/2022/ALC).
文摘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 formaintaining 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.
基金supported by the National Natural Science Foundation of China 82273961(Ming-Wei Wang),82073904(MingWei Wang),81872915(Ming-Wei Wang),82273985(Dehua Yang)and 81973373(Dehua Yang)Shanghai Municipality Science and Technology Development Fund 21JC1401600(Dehua Yang)and 23XD1400900(Dehua Yang)+3 种基金National Science&Technology Major Project of China-Key New Drug Creation and Manufacturing Program 2018ZX09735-001(Ming-Wei Wang)and 2018ZX097110002-002-005(Dehua Yang)STI2030-Major Project 2021ZD0203400(Qingtong Zhou)the National Key Basic Research Program of China 2018YFA0507000(Ming-Wei Wang)Hainan Provincial Major Science and Technology Project ZDKJ2021028(Dehua Yang and Qingtong Zhou)。
文摘To the Editor:G protein-coupled receptors(GPCRs)are the largest group of membrane proteins with over 800 members,characteristic of a seven transmembrane domain1.By playing crucial roles in regulation of various physiological processes,GPCRs have been implicated in many diseases including diabetes,obesity,depression and cancer.To initiate different intracellular responses,GPCRs mainly interact with three families of effector proteins upon agonist binding:the heterotrimeric G proteins,G protein-coupled receptor kinases(GRKs)and arrestins1.
