Suppression of the Prostaglandin I2–Type 1 Interferon Axis Induces Extramedullary Hematopoiesis to Promote Cardiac Repair After Myocardial Infarction

作者：Huizhen Lv, Chenchen Wang, Zening Liu, Meixi Quan, Kan Li, Fanglin Gou, Xuelian Shi, Qian Liu, Ying Yu, Ping Zhu, Hui Cheng, Tao Cheng, Ding Ai · 发表于：Circulation · 年份：2025 · DOI：10.1161/circulationaha.124.069420 · 被引用次数：13 · 研究领域：Cardiac Fibrosis and Remodeling、Congenital heart defects research、Immune cells in cancer

BACKGROUND: Immune cells are closely associated with all processes of cardiac repair after myocardial infarction (MI), including the initiation, development, and resolution of inflammation. Spleen extramedullary hematopoiesis (EMH) serves as a crucial source of emergency mature blood cells that are generated through the self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of EMH in cardiac repair after MI remains unclear. METHODS: To assess the role of spleen EMH in MI, a Tcf21 CreER Scf flox/flox MI mouse model with inhibited EMH was constructed. GFP + (green fluorescent protein) hematopoietic stem cells were sorted from eGFP (enhanced GFP) mouse spleen by flow cytometry and injected into Tcf21 CreER Scf flox/flox mice to test the sources of local inflammatory cells during MI. Using highly specific liquid chromatography–tandem mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the spleen after MI. RESULTS: We found that MI enhanced EMH, as reflected by the increase in spleen weight and volume and the number of HSPCs in the spleen. The lack of EMH in Scf -deficient mice exacerbated tissue injury after MI. Analysis of the transcriptome of spleen HSPCs after MI revealed that the type 1 interferon pathway was substantially inhibited in hematopoietic stem cell /multipotent progenitor subclusters, and the absen...