Platelets sequester extracellular DNA, capturing tumor-derived and free fetal DNA

• 成果类型: Article
• 署名作者: Murphy, Lauren; Inchauspe, Jeanne; Valenzano, Giampiero; Holland, Pamela; Sousos, Nikolaos; Belnoue-Davis, Hayley L.; Li, Rong; Jooss, Natalie J.; Benlabiod, Camelia; Murphy, Eleanor; Etzioni, Zohar; Shepherd, Emelie; Denly, Lucy; Biswas, Sujata; Chen, Lin; O'Sullivan, Jennifer; Rimmer, Michael P.; Khan, Abdullah O.; Karali, Christina Simoglou; Nasreddin, Nadia; Hitchcock, Ian S.; Koupenova, Milka; Kriaucionis, Skirmantas; Hughes, Jim R.; O'Neill, Eric; Vatish, Manu; Rees, Paul; Leedham, Simon; Desborough, Michael; Mead, Adam J.; Schuster-Bockler, Benjamin; Gregory, Christopher D.; Psaila, Bethan
• 署名单位: University of Oxford; University of Oxford; University of Oxford; Ludwig Institute for Cancer Research; University of Oxford; University of Edinburgh; Oxford University Hospitals NHS Foundation Trust; University of Oxford; Wellcome Centre for Human Genetics; University of York - UK; University of York - UK; University of Massachusetts System; University of Massachusetts Worcester; UMass Chan Medical School; University of Oxford; Swansea University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8870
• DOI: 10.1126/science.adp3971
• 发表日期: 2025-08-14
• 关键词: educated platelets; blood-platelets; cancer; expression; identification; exosomes; binding; surface; seq; AGE

摘要

Platelets are anucleate blood cells vital for hemostasis and immunity. During cell death and aberrant mitosis, nucleated cells release DNA, resulting in cell-free DNA in plasma (cfDNA). An excess of cfDNA is deleterious. Given their ability to internalize pathogen-derived nucleic acids, we hypothesized that platelets may also clear endogenous cfDNA. We found that, despite lacking a nucleus, platelets contained a repertoire of DNA fragments mapping across the nuclear genome. We detected fetal DNA in maternal platelets and cancer-derived DNA in platelets from patients with premalignant and cancerous lesions. As current liquid biopsy approaches utilize platelet-depleted plasma, important genetic information contained within platelets is being missed. This study establishes a physiological role for platelets that has not previously been highlighted, with broad translational relevance.