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

Shasha Fan; Chuanliang Guo; Guanheng Yang; Lei Hong; Hongyu Li; Ji Ma; Yiye Zhou; Shuyue Fan; Yan Xue; Fanyi Zeng

doi:10.1016/j.jgg.2024.05.003

Volume 51 Issue 10

Oct. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(10): 1055-1065

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

doi: 10.1016/j.jgg.2024.05.003

Shasha Fan^a,b,c,
Chuanliang Guo^b,c,
Guanheng Yang^b,c,
Lei Hong^b,c,
Hongyu Li^b,c,
Ji Ma^a,b,c,
Yiye Zhou^a,b,c,
Shuyue Fan^a,c,
Yan Xue^a,b,c,
Fanyi Zeng^a,b,c,d

a. Department of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
b. Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China;
c. NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, China;
d. School of Pharmacy, Macau University of Science and Technology, Macau 999078, China

Funds:

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), 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), and the Macau Science and Technology Development fund (FDCT) (0092/2022/A2 and 003/2022/ALC).

Received Date: 2024-02-11
Accepted Date: 2024-05-09
Rev Recd Date: 2024-05-08

Available Online: 2025-06-06

Publish Date: 2024-05-14

Abstract

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 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.
- Embryonic stem cell,
- GPCR,
- GPR160,
- JAK1/STAT3 signaling pathway

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References(62)

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