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

Shasha Fan ¹Chuanliang Guo ²Guanheng Yang ²Lei Hong ²Hongyu Li ²Ji Ma ¹Yiye Zhou ¹Shuyue Fan ³Yan Xue ¹Fanyi Zeng⁴

扫码查看

作者信息

1. 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
2. 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
3. Department of Histo-Embryology,Genetics and Developmental Biology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering,Shanghai 200040,China
4. 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
折叠

Abstract

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.

Key words

Embryonic stem cell/GPCR/GPR160/JAK1/STAT3 signaling pathway

引用本文复制引用

基金项目

National Key Research and Development Program of China(2019YFA0801402)

National Natural Science Foundation of China(82271890)

Shanghai Key Clinical Specialty Project(shslczdzk05705)

Shanghai Top Priority Key Discipline Project(2017ZZ02019)

Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212200)

Macau Science and Technology Development fund(FDCT)(0092/2022/A2)

Macau Science and Technology Development fund(FDCT)(003/2022/ALC)

出版年

2024

遗传学报

中国遗传学会中国科学院遗传与发育生物学研究所

遗传学报

CSTPCDCSCD

影响因子：0.821

ISSN：1673-8527

参考文献量32

段落导航