Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis  

作　　者：Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang 

机构地区：[1]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Peking University,Beijing,100191,China [2]Department of Biomedical Informatics,School of Basic Medical Sciences,Peking University,Beijing,100191,China [3]State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Beijing,100191,China [4]Center for Obesity and Metabolic Disease Research,School of Basic Medical Sciences,Peking University,Beijing,100191,China [5]State Key Laboratory of Female Fertility Promotion,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing,100191,China [6]National Clinical Research Center for Obstetrics and Gynecology,Peking University Third Hospital,Beijing,100191,China [7]Department of Endocrinology and Metabolism,Peking University Third Hospital,Beijing,100191,China [8]Key Laboratory Experimental Teratology of the Ministry of Education,Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Cheeloo College of Medicine,Shandong University,Jinan,250100,China [9]Department of Immunology,School of Basic Medical Sciences,Peking University,Beijing,100191,China [10]Center of Basic Medical Research,Institute of Medical Innovation and Research,Peking University Third Hospital,Beijing,100191,China

出　　处：《Science China(Life Sciences)》2025年第4期1057-1072,共16页中国科学(生命科学英文版)

基　　金：supported by the National Natural Science Foundation of China(32270603,31925021,82130022,92357305,82341226,32271232);the National Key Research and Development Program of China(2021YFF1201100,2018YFA0800701);the Fundamental Research Funds for the Central Universities(BMU2021YJ057)。

摘　　要：Adipogenesis is the healthy expansion of white adipose tissue(WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the body.Therefore,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors(GPCRs),holds significant clinical promise.These receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with obesity.We utilized trajectory inference methods to analyze three distinct single-nucleus sequencing(sNuc-seq)datasets of adipose tissue and systematically identified GPCRs with the potential to regulate adipogenesis.Through verification in primary adipose progenitor cells(APCs)of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this process.In the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic dysfunction.Additionally,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors(TFs)MEF2D and TCF12 regulated the expression of ADGRD1 and GPR39,respectively.Our study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

关 键 词：ADIPOGENESIS GPCRS trajectory inference 

分 类 号：R589.2[医药卫生—内分泌]