上海交通大学医学院Fanyi Zeng和Yan Xue合作，近期取得重要工作进展。他们研究发现，GPR160通过JAK1/STAT3信号通路调控小鼠胚胎干细胞的自我更新和多能性。相关研究成果2024年5月14日在线发表于《遗传学报》杂志上。

据介绍，G蛋白偶联受体（GPCR）是最大的跨膜受体家族，调节多种生理和病理过程。尽管进行了广泛的研究，但GPCR在小鼠胚胎干细胞（mESC）中的作用仍存在显著的数据缺口。

研究人员发现 GPR160（GPCR 的 A 类成员）在 mESC 体外分化成胚状体的过程中被显著下调。敲低GPR160导致多能性相关转录因子的表达下调和谱系标记物的表达上调，同时mESC细胞周期停滞在G0/G1期。RNA-seq分析显示，GPR160参与对维持ESC干性至关重要的JAK/STAT信号通路，GPR160的敲低导致STAT3磷酸化水平的下调，而STAT3的磷酸化水平又被一种STAT3激活剂colivelin部分挽救。GPR160与JAK1物理相互作用，并与白血病抑制因子受体（LIFR）和gp130协同激活STAT3通路。

总之，这一结果表明，GPR160通过与JAK1-LIFR-gp130复合物相互作用介导JAK1/STAT3信号通路来调节mESC的自我更新和多能性。

附：英文原文

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

Author: Yan Xue a b c, Fanyi Zeng a b c d

Issue&Volume: 2024/05/14

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) represent a significant data gap. 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. Constant 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.

DOI: 10.1016/j.jgg.2024.05.003

Source: https://www.sciencedirect.com/science/article/pii/S1673852724001048