ArticleNature communications2017
Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification.
Article in Nature communications, 2017. 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 185 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
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 285 citations in OpenAlex.
- Single-Cell Meta-Analysis Uncovers the Pancreatic Endothelial Cell Transcriptomic Signature and Reveals a Key Role for NKX2-3 in PLVAP Expression.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- From Somatic Driver to Molecular Therapy in Retinal, Choroidal and Periocular Vascular Disease: Mosaicism, Targetable Pathways and Ocular Toxicity.International journal of molecular sciences · 2026Review
- Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Gene-Specific Endothelial Programs Drive AVM Pathogenesis inArteriosclerosis, thrombosis, and vascular biology · 2026Article
- A microphysiological system HHT-on-a-chip platform recapitulates patient vascular lesions.Nature communications · 2026Article
- Human Cell-Derived Extracellular Matrix Modulates Endothelial Cell Morphology and Metabolism in Response to Fluid Shear Stress.ACS biomaterials science & engineering · 2026Article
- Coronary endothelial cells undergo venous-enriched disrupted maturation following myocardial infarction.Basic research in cardiology · 2026Article
- A noncanonical role for Jagged1 in endothelial mechanotransduction.The FEBS journal · 2026Article
- Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.Science China. Life sciences · 2026Review
- Regulation of endothelial cell chromatin availability and transcription factor activity during arterial-venous specification.Development (Cambridge, England) · 2026Article
- Genetic determinants of insufficiency of the collateral circulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Mechanical Signaling Regulates DNA Methylation to Maintain Muscle Stem Cell Quiescence.bioRxiv : the preprint server for biology · 2026Article
- A Perturb-seq screen guided by species divergence uncovers pathways for collateral artery formation.bioRxiv : the preprint server for biology · 2026Article
- Retinoic acid regulates fetoplacental vascularization via notch signaling and a SEMA3E/F-PLEXIND1 axis.iScience · 2026Article
- The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress.Life science alliance · 2026Article
- Prdm16 Amplifies Notch Signaling and Suppresses Venous Lineage Specification to Prevent Arteriovenous Malformations During Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Micropatterning transcriptionally and phenotypically reprograms endothelial cells.Acta biomaterialia · 2026Article
- Diverse roles of connexins in the neuro-vasculature in homeostasis and disease.Translational neuroscience · 2026Review
- Flow-induced Klf4-Akt signaling links EC cycling to mural cell defects in arterial-venous malformations.Theranostics · 2026Article
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
125 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Establishment of a functional vascular network is rate-limiting in embryonic development, tissue repair and engineering. During blood vessel formation, newly generated endothelial cells rapidly expand into primitive plexi that undergo vascular remodeling into circulatory networks, requiring coordinated growth inhibition and arterial-venous specification. Whether the mechanisms controlling endothelial cell cycle arrest and acquisition of specialized phenotypes are interdependent is unknown. Here we demonstrate that fluid shear stress, at arterial flow magnitudes, maximally activates NOTCH signaling, which upregulates GJA4 (commonly, Cx37) and downstream cell cycle inhibitor CDKN1B (p27). Blockade of any of these steps causes hyperproliferation and loss of arterial specification. Re-expression of GJA4 or CDKN1B, or chemical cell cycle inhibition, restores endothelial growth control and arterial gene expression. Thus, we elucidate a mechanochemical pathway in which arterial shear activates a NOTCH-GJA4-CDKN1B axis that promotes endothelial cell cycle arrest to enable arterial gene expression. These insights will guide vascular regeneration and engineering.
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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.