ArticleBlood2010
An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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.
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Who cites it
49 citing papers in PubMed, 101 citations in OpenAlex.
- Compartment-specific regulation of stromal differentiation of the spleen in health and disease.Genes and immunity · 2026Review
- Changes in vascular identity during vascular remodeling.JVS-vascular science · 2025Article
- The role of MAPK, notch and Wnt signaling pathways in papillary thyroid cancer: Evidence from a systematic review and meta-analyzing microarray datasets employing bioinformatics knowledge and literature.Biochemistry and biophysics reports · 2024Article
- Synthetic hyaluronic acid coating preserves the phenotypes of lymphatic endothelial cells.Biomaterials science · 2023Article
- Single-cell analysis of lymphatic endothelial cell fate specification and differentiation during zebrafish development.The EMBO journal · 2023Article
- Lymphatic vasculature in the central nervous system.Frontiers in cell and developmental biology · 2023Review
- Endothelial Cell Fate Determination: A Top Notch Job in Vascular Decision-Making.Cold Spring Harbor perspectives in medicine · 2022Review
- The NOTCH4-GATA4-IRG1 axis as a novel target in early-onset colorectal cancer.Cytokine & growth factor reviews · 2022Review
- The Role of Podoplanin in the Immune System and Inflammation.Journal of inflammation research · 2022Review
- A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development.BMB reports · 2021Review
- The Lymphatic System in Zebrafish Heart Development, Regeneration and Disease Modeling.Journal of cardiovascular development and disease · 2021Review
- Editorial: Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity.Frontiers in cell and developmental biology · 2021Article
- Article
- Cell Fate Determination of Lymphatic Endothelial Cells.International journal of molecular sciences · 2020Review
- Review
- Article
- COUP-TFII in Health and Disease.Cells · 2019Review
- Podoplanin in Inflammation and Cancer.International journal of molecular sciences · 2019Review
- Molecular identity of arteries, veins, and lymphatics.Journal of vascular surgery · 2019Review
- Complex Non-sinus-associated Pachymeningeal Lymphatic Structures: Interrelationship With Blood Microvasculature.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Arteriovenous-lymphatic endothelial cell fates are specified by the master regulators, namely, Notch, COUP-TFII, and Prox1. Whereas Notch is expressed in the arteries and COUP-TFII in the veins, the lymphatics express all 3 cell fate regulators. Previous studies show that lymphatic endothelial cell (LEC) fate is highly plastic and reversible, raising a new concept that all 3 endothelial cell fates may co-reside in LECs and a subtle alteration can result in a reprogramming of LEC fate. We provide a molecular basis verifying this concept by identifying a cross-control mechanism among these cell fate regulators. We found that Notch signal down-regulates Prox1 and COUP-TFII through Hey1 and Hey2 and that activated Notch receptor suppresses the lymphatic phenotypes and induces the arterial cell fate. On the contrary, Prox1 and COUP-TFII attenuate vascular endothelial growth factor signaling, known to induce Notch, by repressing vascular endothelial growth factor receptor-2 and neuropilin-1. We show that previously reported podoplanin-based LEC heterogeneity is associated with differential expression of Notch1 in human cutaneous lymphatics. We propose that the expression of the 3 cell fate regulators is controlled by an exquisite feedback mechanism working in LECs and that LEC fate is a consequence of the Prox1-directed lymphatic equilibrium among the cell fate regulators.
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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.