Multi-omics reveals the switch role of abnormal methylation in the regulation of decidual macrophages function in recurrent spontaneous abortion

作者全名："Li, Qian; Zhang, Lei; Zou, Hua; Chai, Tingjia; Su, Yan; Shen, Yan; He, Xiao; Qi, Hongbo; Li, Chunli"

作者地址："[Li, Qian; Zhang, Lei; Zou, Hua; Su, Yan; Shen, Yan; He, Xiao; Li, Chunli] Chongqing Med Univ, Dept Clin Lab, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Li, Qian; Zhang, Lei; Zou, Hua; Su, Yan; Shen, Yan; He, Xiao; Qi, Hongbo; Li, Chunli] Chongqing Hlth Ctr Women & Children, Dept Clin Lab, Chongqing 401174, Peoples R China; [Qi, Hongbo] Chongqing Med Univ, Dept Obstet & Gynecol, Women & Childrens Hosp, Chongqing, Peoples R China; [Qi, Hongbo] Chongqing Hlth Ctr Women & Children, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Chai, Tingjia] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrine Lab, Chongqing, Peoples R China"

通信作者："Qi, HB; Li, CL (通讯作者)，Chongqing Hlth Ctr Women & Children, Dept Clin Lab, Chongqing 401174, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001178351700001

JCR分区：Q2

影响因子：4.4

年份：2024

卷号：117

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Recurrent spontaneous abortion; Decidual macrophages; DNA methylation; Single -cell RNA sequencing; Interferon regulatory factor 7; STAT1

摘要："RSA, recurrent spontaneous abortion, often causes serious physical damage and psychological pressure in reproductive women with unclarified pathogenesis. Abnormal function of decidual cells and aberrant DNA methylation have been reported to cause RSA, but their association remains unclear. Here, we integrated transcriptome, DNA methylome, and scRNA-seq to clarify the regulatory relationship between DNA methylation and decidual cells in RSA. We found that DNA methylation mainly influenced the function of decidual macrophages (DMs), of which four hub genes, HLA-A, HLA-F, SQSTM1/P62, and Interferon regulatory factor 7 (IRF7), related to 22 hypomethylated CpG sites, regulated 16 hub pathways to participate in RSA pathogenesis. In particular, using transcription factor analysis, it is suggested that the upregulation of IRF7 transcription was associated with enhanced recruitment of the transcription factor STAT1 by the hypomethylated promoter region of IRF7. As the current research on DNA methylation of macrophages in the uterine microenvironment of RSA is still blank, our systematic picture of abnormal DNA methylation in regulating DM function provides new insights into the role of DNA methylation in RSA occurrence, which may aid in further prevention and treatment of RSA."

基金机构："Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission [CSTB2023NSCQ-BHX0025]"

基金资助正文："This work was supported by the Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission (CSTB2023NSCQ-BHX0025) ."