ReviewAnnals of the New York Academy of Sciences2016
Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling.
Review in Annals of the New York Academy of Sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
19 citing papers in PubMed, 28 citations in OpenAlex.
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- An interactive resource of molecular signalling in the developing human haematopoietic stem cell niche.Development (Cambridge, England) · 2023Article
- Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.Thrombosis and haemostasis · 2023Article
- Emerging Evidence of the Significance of Thioredoxin-1 in Hematopoietic Stem Cell Aging.Antioxidants (Basel, Switzerland) · 2022Review
- The endothelial protein C receptor plays an essential role in the maintenance of pregnancy.Science advances · 2020Article
- Mechanisms and rejuvenation strategies for aged hematopoietic stem cells.Journal of hematology & oncology · 2020Review
- Ex vivo HSC expansion challenges the paradigm of unidirectional human hematopoiesis.Annals of the New York Academy of Sciences · 2020Review
- Limited Mitochondrial Activity Coupled With Strong Expression of CD34, CD90 and EPCR Determines the Functional Fitness ofFrontiers in cell and developmental biology · 2020Article
- CD34 and EPCR coordinately enrich functional murine hematopoietic stem cells under normal and inflammatory conditions.Experimental hematology · 2020Article
- Nitric Oxide in the Control of theFrontiers in cell and developmental biology · 2020Article
- Review
- UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal.PloS one · 2019Article
- A revised road map for the commitment of human cord blood CD34-negative hematopoietic stem cells.Nature communications · 2018Article
- Neoplasms in the bone marrow niches: disturbance of the microecosystem.International journal of hematology · 2017Review
- Adhesion Assay for Murine Bone Marrow Hematopoietic Stem Cells.Bio-protocol · 2017Article
- Article
- Effects of cognate, non-cognate and synthetic CXCR4 and ACKR3 ligands on human lung endothelial cell barrier function.PloS one · 2017Article
- Current Understanding of the Pathways Involved in Adult Stem and Progenitor Cell Migration for Tissue Homeostasis and Repair.Stem cell reviews and reports · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/protease-activated receptor-1 (PAR1) signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR(+) LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NO(low) LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling that overcomes BM EPCR(+) LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production.
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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.