Setdb1 ablation in macrophages attenuates fibrosis in heart allografts

• 成果类型: Article
• 署名作者: Ma, Zhibo; Zhou, Xi; Jia, Wenlong; Tan, Xiaosheng; Huang, Xia; Wang, Jingzeng; Sun, Lingjuan; Li, Qingwen; Zhao, Xiangli; Yuan, Naonao; Liu, Ping; Liu, Jing; Chen, Zhishui; Lan, Peixiang; Nathan, Carl F.
• 署名单位: Huazhong University of Science & Technology; Chinese Academy of Medical Sciences - Peking Union Medical College; Huazhong University of Science & Technology; Huazhong University of Science & Technology
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8951
• DOI: 10.1073/pnas.2424534122
• 发表日期: 2025-07-01
• 关键词: single-cell

摘要

Tissue fibrosis is commonly associated with organ malfunction and is strongly associated with the development of chronic rejection, cardiovascular diseases, and other chronic diseases. Fibrosis also contributes to immune exclusion in tumor tissues. Targeting fibrosis might be a strategy for prolonging allograft survival while suppressing cancer development. Here, single- cell transcriptomes of human and mouse heart allografts showed that macrophages accumulated in grafts with fibrosis were reprogrammed via histone methylation regulated by Setdb1, an H3K9 methyltransferase. Myeloid- specific heart allografts and tumor tissues in mice. Our single- cell sequencing data showed that PIRA receptors. Blocking the interaction between FN1 and these receptors inhibited fibrosis in allograft and tumor tissues. Our results reveal a target, histone methylation in macrophages, for the treatment of fibrosis- related disease.