Transcriptome Analysis IdentifiedSPP1+Monocytes as a Key in Extracellular Matrix Formation in Thrombi

Abstract

AbstractThrombi 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 identifiedSPP1as 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 betweenSPP1-high monocytes/macrophages and fibroblasts. These data suggest thatSPP1-high monocytes/macrophages play a crucial role in extracellular matrix formation in thrombi and provide a basis for new antithrombotic therapies targeting thrombus maturation.TeaserSPP1+monocytes play a key role in thrombus maturation, which can be a potential target for novel antithrombotic therapies.