ArticleBlood2010
Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
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Who cites it
204 citing papers in PubMed, 424 citations in OpenAlex.
- Soluble CLEC-2 is generated independently of ADAM10 and is increased in plasma in acute coronary syndrome: comparison with soluble GPVI.International journal of hematology · 2019Trial
- Soluble CLEC-2 as an Emerging Biomarker of In Vivo Platelet Activation.Journal of clinical medicine · 2026Review
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Podoplanin-positive extracellular vesicles in ovarian cancer: linking thrombosis, platelet crosstalk, and cancer stemness - a narrative review.Annals of medicine and surgery (2012) · 2026Article
- Beyond Hemostasis: Platelets' Multifaceted Functions in Immune Responses.Life (Basel, Switzerland) · 2026Review
- Partial downregulation of platelet glycoprotein VI by low affinity antibodies confers sustained and safe antithrombotic protection.Signal transduction and targeted therapy · 2026Article
- The Plasma Glycoprotein Milieu in the Hemato-Oncological Patient Inhibits Platelet Function.Biomolecules · 2026Article
- Endothelial von Hippel-Lindau gene deletion causes abnormal blood and lymphatic vasculature through ectopic activation of the HIF-CXCR4 axis.Development (Cambridge, England) · 2026Article
- Platelets as immune sensors: monitoring immune dynamics and diagnosing disease states across multiple disorders.EBioMedicine · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Humanized murine models of platelet function.Current opinion in hematology · 2025Review
- Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs.Nature communications · 2025Article
- Mice with lymphatic dysfunction develop pathogenic lung tertiary lymphoid organs that model an autoimmune emphysema phenotype of COPD.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.EMBO reports · 2024Review
- A novel therapy for fracture healing by increasing lymphatic drainage.Journal of orthopaedic translation · 2024Article
- Abnormalities in C-type lectin-like receptor 2 in a patient with Gorham-Stout disease: the first case report.Research and practice in thrombosis and haemostasis · 2024Article
- Recent Advances in Therapeutic Modalities Against Breast Cancer-Related Lymphedema: Future Epigenetic Landscape.Lymphatic research and biology · 2023Review
- De novo hematopoiesis from the fetal lung.Blood advances · 2023Article
- Platelet functional abnormalities in pediatric patients with kaposiform hemangioendothelioma/Kasabach-Merritt phenomenon.Blood advances · 2023Article
- Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.Blood advances · 2023Article
144 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
Although platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK-SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre-mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76-dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.