Integrative single-cell RNA and ATAC sequencing reveals that the FOXO1-PRDX2-TNF axis regulates tendinopathy

作者全名："Guo, Junfeng; Tang, Hong; Huang, Pan; Ye, Xiao; Tang, Chuyue; Shu, Zhao; Guo, Junfeng; Kang, Xia; Shi, Youxing; Zhou, Binghua; Liang, Taotao; Tang, Kanglai"

作者地址："[Guo, Junfeng; Tang, Hong; Huang, Pan; Ye, Xiao; Tang, Chuyue; Kang, Xia; Shi, Youxing; Zhou, Binghua; Liang, Taotao; Tang, Kanglai] Third Mil Med Univ, Southwest Hosp, Sports Med Ctr, Dept Orthoped,State Key Lab Trauma Burn & Combined, Chongqing, Peoples R China; [Shu, Zhao] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Chongqing, Peoples R China; [Guo, Junfeng] 970th Hosp Joint Logist Support Force, Dept Stomatol, Yantai, Peoples R China"

通信作者："Zhou, BH; Liang, TT; Tang, KL (通讯作者)，Third Mil Med Univ, Southwest Hosp, Sports Med Ctr, Dept Orthoped,State Key Lab Trauma Burn & Combined, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000991547000001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：tendinopathy; single-cell multi-modal analysis; microenvironment; harmful cells; Prdx2

摘要："IntroductionTendinopathy, the most common form of chronic tendon disorder, leads to persistent tendon pain and loss of function. Profiling the heterogeneous cellular composition in the tendon microenvironment helps to elucidate rational molecular mechanisms of tendinopathy. Methods and resultsIn this study, through a multi-modal analysis, a single-cell RNA- and ATAC-seq integrated tendinopathy landscape was generated for the first time. We found that a specific cell subpopulation with low PRDX2 expression exhibited a higher level of inflammation, lower proliferation and migration ability, which not only promoted tendon injury but also led to microenvironment deterioration. Mechanistically, a motif enrichment analysis of chromatin accessibility showed that FOXO1 was an upstream regulator of PRDX2 transcription, and we confirmed that functional blockade of FOXO1 activity induced PRDX2 silencing. The TNF signaling pathway was significantly activated in the PRDX2-low group, and TNF inhibition effectively restored diseased cell degradation. DiscussionWe revealed an essential role of diseased cells in tendinopathy and proposed the FOXO1-PRDX2-TNF axis is a potential regulatory mechanism for the treatment of tendinopathy."

基金机构："National Natural Science Foundation of China [82072516, 82130071, 82102635]; Personalization Training Program for the Training Object of the Outstanding Talents of Army Medical University [csts2020jcyj-cxttX0004]; Sports Injury Repair Research and Innovation Group; [4139Z2C2]"

基金资助正文："This research was supported by grants from the National Natural Science Foundation of China (nos. 82072516, 82130071 and 82102635), Sports Injury Repair Research and Innovation Group (csts2020jcyj-cxttX0004) and the Personalization Training Program for the Training Object of the Outstanding Talents of Army Medical University (4139Z2C2)."