ArticleJCI insight2025
A single-cell atlas of normal and KRASG12D-malformed lymphatic vessels.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- RAS-PI3Kα signaling regulates KrasG12D-induced lymphangiogenesis in complex lymphatic anomalies.Disease models & mechanisms · 2026Article
- The crosstalk between lymphatic endothelial cells and immune cells in Physiological and Pathological conditions.Cellular and molecular life sciences : CMLS · 2026Review
- Spatially Resolved Heterogeneity of Lymphatic Vasculature in the Adult Lung-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- VEGF-D-induced intraosseous lymphangiogenesis drives site-specific heterotopic bone resorption.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lymphatic Malformations With Activating KRAS Mutations Impair Lymphatic Valve Development Through Matrix Metalloproteinases.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Targeting lymphatic vessels enhances bone regeneration by augmenting osteoclast activity in mouse models of amputation.The Journal of clinical investigation · 2026Article
- Normal cardiac lymphatics and their mimics.American journal of physiology. Heart and circulatory physiology · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
Somatic activating mutations in KRAS can cause complex lymphatic anomalies (CLAs). However, the specific processes that drive KRAS-mediated CLAs have yet to be fully elucidated. Here, we used single-cell RNA sequencing to construct an atlas of normal and KrasG12D-malformed lymphatic vessels. We identified 6 subtypes of lymphatic endothelial cells (LECs) in the lungs of adult wild-type mice (Ptx3, capillary, collecting, valve, mixed, and proliferating). To determine when the LEC subtypes were specified during development, we integrated our data with data from 4 stages of development. We found that proliferating and Ptx3 LECs were prevalent during early lymphatic development and that collecting and valve LECs emerged later in development. Additionally, we discovered that the proportion of Ptx3 LECs decreased as the lymphatic network matured but remained high in KrasG12D mice. We also observed that the proportion of collecting and valve LECs was lower in KrasG12D mice than in wild-type mice. Last, we found that immature lymphatic vessels in young mice were more sensitive to the pathologic effects of KrasG12D than mature lymphatic vessels in older mice. Together, our results expand the current model for the development of the lymphatic system and suggest that KRAS mutations impair the maturation of lymphatic vessels.
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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.