ArticleNature medicine2015
PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
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- Scalable quantification of dynamic subcellular spatial organization in single cells across tissues.Research square · 2026Article
- Transcriptional heterogeneity predicts and enables clonal selection in ageing haematopoiesis.Research square · 2026Article
- Epigenetic programming by H3K23ac defines lineage fate of Meg3Nature cell biology · 2026Article
- Review
- Detrimental Effect of Plasma From Patients With Severe Aortic Stenosis on Valvular Endothelial Cells: Role of Proinflammatory Cytokines and Factor Xa.Journal of the American Heart Association · 2026Article
- IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion.eLife · 2025Article
- Cell polarity: cell type-specific regulators, common pathways, and polarized vesicle transport.Leukemia · 2025Review
- Decreased non-neurogenic acetylcholine in bone marrow triggers age-related defective stem/progenitor cell homing.Nature communications · 2025Article
- NO-immune privilege for hematopoietic stem cells.Cell research · 2025Article
- Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.Nature immunology · 2025Article
- Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury.Bioactive materials · 2025Article
- Thrombomodulin: A key regulator of intravascular blood coagulation, fibrinolysis, and inflammation, and a treatment for disseminated intravascular coagulation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Article
- The Concept of Thromboinflammation.Hamostaseologie · 2024Review
- Deciphering the evolving niche interactome of human hematopoietic stem cells from ontogeny to aging.Frontiers in molecular biosciences · 2024Article
- Rivaroxaban attenuates neutrophil maturation in the bone marrow niche.Basic research in cardiology · 2023Article
- Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-α-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conversely, bone marrow blood vessels provide a microenvironment enriched with activated protein C (aPC) that retains EPCR(+) LT-HSCs by limiting NO generation, reducing Cdc42 activity and enhancing integrin VLA4 affinity and adhesion. Inhibition of NO production by aPC-EPCR-PAR1 signaling reduces progenitor cell egress from the bone marrow, increases retention of bone marrow NO(low) EPCR(+) LT-HSCs and protects mice from chemotherapy-induced hematological failure and death. Our study reveals new roles for PAR1 and EPCR in controlling NO production to balance maintenance and recruitment of bone marrow EPCR(+) LT-HSCs, with potential clinical relevance for stem cell transplantation.
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What OpenQuestion holds
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.