Authors
Runze Li, Yuyi Chen, Yuanyuan Song, Ao Zhang, Tuliang Liang, Lirong Lian, Jianing Mi, Nanjie Zhou, Jingrong Wang, Yingnan Bai, Hudan Pan, Quan Liu, Yicheng Zhao, Liang Liu
Published in
Pharmacological research. Pages 108378. Aug 11, 2026. Epub Aug 11, 2026.
Abstract
Platelets have been increasingly recognized as versatile regulators of ageing, immunity, and cancer, yet their functional heterogeneity has remained poorly defined. We performed the first large-scale single-cell RNA sequencing of 28,192 platelets from healthy, aged, metastatic, and treated mice using the BD Rhapsody platform. Our analysis revealed four conserved and functionally distinct platelet transcriptional states: haemostatic platelet (HP), neural gene-enriched platelet (NEP), platelet-leukocyte aggregate (PLA) and platelet-erythrocyte aggregate (PEA). Among these states, Tpm2-high HP is linked to ageing-associated lung metastasis and is characterized by cytoskeletal remodelling gene signatures. The PLA state was predicted to be a signalling hub for immunothrombosis, with a PLA-Bridge subpopulation coordinating immune-adherent platelets via the Ppbp-Cxcl2 and Thbs1-Cd47 checkpoint axes. Strikingly, AAV-mPf4 gene therapy was associated with a neural gene-enriched platelet-associated transcriptional program, which mitigates age-related functional decline. This study provides a single-cell transcriptomic atlas of murine platelets under ageing and metastasis conditions and reveals transcriptional state-specific heterogeneity. This study also proposes PF4-based interventions and cytoskeletal candidates for diagnosis and therapy.
PMID:
42580391
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.
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