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

• DOI: 10.1161/circulationaha.124.069420
• Publication Date: 2025-04-28T09:00:47Z
• Authors: 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
• Keywords: Extramedullary hematopoiesis

BACKGROUND: Immune cells are closely associated with all processes of cardiac repair after myocardial infarction (MI), including the initiation, development, and resolution inflammation. Spleen extramedullary hematopoiesis (EMH) serves as a crucial source emergency mature blood that generated through self-renewal differentiation hematopoietic stem/progenitor (HSPCs). However, how EMH responds to MI role in remains unclear. METHODS: To assess spleen MI, Tcf21 CreER Scf flox/flox mouse model inhibited was constructed. GFP + (green fluorescent protein) stem were sorted from eGFP (enhanced green by flow cytometry injected into mice test sources local inflammatory during MI. Using highly specific liquid chromatography–tandem mass spectrometry single-cell RNA sequencing, we analyzed lipidomic profile arachidonic acid metabolites transcriptomes HSPCs RESULTS: We found enhanced EMH, reflected increase weight volume number spleen. The lack -deficient exacerbated tissue injury Analysis transcriptome revealed type 1 interferon pathway substantially cell/multipotent progenitor subclusters, absence signaling MI-induced EMH. Lipidomics analysis prostaglandin I2 (PGI2) markedly reduced PGI2 suppressed receptor (IP)–cyclic adenosine monophosphate– 453 p-SP1 cascade HSPCs. Hematopoietic cell–specific IP-deficient exhibited improved recovery CONCLUSIONS: Together, our findings PGI2–IFN axis involved providing new mechanistic insights offering therapeutic target for treating ischemic injury.