Integrating spatial transcriptomics and single-nucleus RNA-seq revealed the specific inhibitory effects of TGF-β on intramuscular fat deposition  

作　　者：Xiaoyu Wang Chuchu Chen Chenggan Li Xiaochang Chen Rong Xu Meilin Chen Yongpeng Li Yihao Liu Xiaohong Liu Yaosheng Chen Delin Mo 

机构地区：[1]State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou 510006,China [2]Shaanxi Basic and Clinical Translational Research Team for Atherosclerotic Cardiovascular Disease,Shaanxi Key Laboratory of Ischemic Cardiovascular Disease,Institute of Basic and Translational Medicine,Xi’an Medical University,Xi’an 710021,China

出　　处：《Science China(Life Sciences)》2025年第3期746-763,共18页中国科学(生命科学英文版)

基　　金：supported by the National Natural Science Foundation of China(323B2058);Selection and Breeding of New Local Pig Breeds and Promotion of Industrialization(2022-440000-43010101-9501);Selection and Breeding of Guangdong Small-ear Spotted Pig(2022-440000-4301030202-9510);China Agriculture Research System(CASR-35);the Key Scientific Research Project of Education Department of Shaanxi(22JS033).

摘　　要：Intramuscular fat(IMF)is a complex adipose tissue within skeletal muscle,appearing specially tissue heterogeneous,and the factors influencing its formation remain unclear.In conditions such as diabetes,aging,and muscle wasting,IMF was deposited in abnormal locations in skeletal muscle,damaged the normal physiological functions of skeletal muscle.Here,we used Longissimus dorsi muscles from pigs with different IMF contents as samples and adopted a method combining spatial transcriptome(ST)and single-nucleus RNA-seq to identify the spatial heterogeneity of IMF.ST revealed that genes involved in TGF-βsignaling pathways were specifically highly enriched in IMF.In lean pigs,IMF autocrine produces more TGF-β2,while in obese pigs,IMF received more endothelial-derived TGF-β1.In vitro experiments have proven that porcine endothelial cells in a simulated high-fat environment released more TGF-β1 than TGF-β2.Moreover,under obesity mice,the addition of TGF-βafter muscle injury abolished IMF production and slowed muscle repair,whereas TGF-βinhibition accelerated muscle repair.Our findings demonstrate that the TGF-βpathway specifically regulates these processes,suggesting it as a potential therapeutic target for managing muscle atrophy in obese patients and enhancing muscle repair while reducing IMF deposition.

关 键 词：intramuscular fat muscle atrophy spatial transcriptome single-nucleus RNA-seq TGF-Β 

分 类 号：R589.2[医药卫生—内分泌]