Transcriptome Analysis Identified SPP1+ Monocytes as a Key in Extracellular Matrix Formation in Thrombi

Thrombi follow various natural courses. They are known to become harder over time and may persist long-term; some of them can also undergo early spontaneous dissolution and disappearance. Hindering thrombus stability may contribute to the treatment of thrombosis and the prevention of embolisms. However, the detailed mechanisms underlying thrombus maturation remain unknown. Using RNA sequencing, we revealed the transcriptional landscape of thrombi retrieved from the cerebral vessels and identified SPP1 as a hub gene related to extracellular matrix formation. Immunohistochemistry confirmed the expression of osteopontin in monocytes/macrophages in the thrombi, particularly in older thrombi. Single-cell RNA sequencing of thrombi from the pulmonary artery revealed increased communication between SPP1 -high monocytes/macrophages and fibroblasts. These data suggest that SPP1 -high monocytes/macrophages play a crucial role in extracellular matrix formation in thrombi and provide a basis for new antithrombotic therapies targeting thrombus maturation. Teaser SPP1+ monocytes play a key role in thrombus maturation, which can be a potential target for novel antithrombotic therapies. ### Competing Interest Statement The authors have declared no competing interest.