ArticleStem cells (Dayton, Ohio)2012
An endogenous vitamin K-dependent mechanism regulates cell proliferation in the brain subventricular stem cell niche.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06817512 (Health Effects of Vitamin K2 Supplementation on Skeletal Muscle and Neurological Function After Ischemic Stroke), which is not on this map. Cited by 26 papers.
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.
Health Effects of Vitamin K2 Supplementation on Skeletal Muscle and Neurological Function After Ischemic Stroke
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Integration of Metabolic Pathways and Micronutrient Signals Influences Neurodevelopment by Modulating Neural Stem Cell Dynamics.Molecular neurobiology · 2026Review
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- Adult neural stem cells mediate hippocampal synapse elimination for circuit homeostasis through MERTK.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- GAS6 as a potential target to alleviate neuroinflammation during Japanese encephalitis in mouse models.Journal of neuroinflammation · 2024Article
- The Vitamin K-Dependent Anticoagulant Factor, Protein S, Regulates Vascular Permeability.Current issues in molecular biology · 2024Article
- Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies.Frontiers in cellular and infection microbiology · 2022Review
- TAM Signaling in the Nervous System.Brain plasticity (Amsterdam, Netherlands) · 2021Article
- Vitamin K3 derivative induces apoptotic cell death in neuroblastoma via downregulation of MYCN expression.Biochemistry and biophysics reports · 2019Article
- Article
- TAM Receptor Pathways at the Crossroads of Neuroinflammation and Neurodegeneration.Disease markers · 2019Review
- The role of TAM family receptors and ligands in the nervous system: From development to pathobiology.Pharmacology & therapeutics · 2018Review
- Migration/Invasion of Malignant Gliomas and Implications for Therapeutic Treatment.International journal of molecular sciences · 2018Review
- Cancer Stem Cells: Emergent Nature of Tumor Emergency.Frontiers in genetics · 2018Article
- The tyrosine kinase receptor Tyro3 enhances lifespan and neuropeptide Y (Npy) neuron survival in the mouse anorexia (Disease models & mechanisms · 2017Article
- Protein S Negatively Regulates Neural Stem Cell Self-Renewal through Bmi-1 Signaling.Frontiers in molecular neuroscience · 2017Article
- Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.Oncotarget · 2016Article
- Membrane Cholesterol Modulates Superwarfarin Toxicity.Biophysical journal · 2016Article
- Review
- Small molecule inhibition of Axl receptor tyrosine kinase potently suppresses multiple malignant properties of glioma cells.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neural stem cells (NSC) persist in the adult mammalian brain, within the subventricular zone (SVZ). The endogenous mechanisms underpinning SVZ stem and progenitor cell proliferation are not fully elucidated. Vitamin K-dependent proteins (VKDPs) are mainly secreted factors that were initially discovered as major regulators of blood coagulation. Warfarin ((S(-)-3-acetonylbenzyl)-4-hydroxycoumarin)), a widespread anticoagulant, is a vitamin K antagonist that inhibits the production of functional VKDP. We demonstrate that the suppression of functional VKDPs production, in vitro, by exposure of SVZ cell cultures to warfarin or, in vivo, by its intracerebroventricular injection to mice, leads to a substantial increase in SVZ cell proliferation. We identify the anticoagulant factors, protein S and its structural homolog Gas6, as the two only VKDPs produced by SVZ cells and describe the expression and activation pattern of their Tyro3, Axl, and Mer tyrosine kinase receptors. Both in vitro and in vivo loss of function studies consisting in either Gas6 gene invalidation or in endogenous protein S neutralization, provided evidence for an important novel regulatory role of these two VKDPs in the SVZ neurogenic niche. Specifically, we show that while a loss of Gas6 leads to a reduction in the numbers of stem-like cells and in olfactory bulb neurogenesis, endogenous protein S inhibits SVZ cell proliferation. Our study opens up new perspectives for investigating further the role of vitamin K, VKDPs, and anticoagulants in NSC biology in health and disease.
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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.