FOXC2 controls adult lymphatic endothelial specialization, function, and gut lymphatic barrier preventing multiorgan failure
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loss skewed the specialization of lymphatic endothelial subsets, leading to populations with mixed, pro-fibrotic identities and to emergence of lymph node-like endothelial cells. Our study uncovers a cross-talk between lymphatic vascular function and commensal microbiota, provides single-cell atlas of lymphatic endothelial subtypes, and reveals organ-specific and systemic effects of dysfunctional lymphatics. These effects potentially contribute to the pathogenesis of diseases, such as inflammatory bowel disease, cancer, or lymphedema.
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Single-cell transcriptome analyses of inguinal-axillary collecting LVs from the mouse show multiple clusters of cells with molecular markers delineating cell types: Prox1+ LECs, PDGFRα+ fibroblast-like cells, Myh11+ LMCs, and immune cells.
“Single-cell transcriptome analyses of inguinal-axillary collecting LVs from the mouse show multiple clusters of cells with molecular markers delineating these cell types: a large cluster of Prox1 + LECs, a heterogeneous cluster of PDGFRα + fibroblast-like cells, a cluster of Myh11 + LMCs, and multiple clusters of immune cells (14, 15).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [15]
The Results section, “Single-cell transcriptome analysis defines molecular features of adult LEC functional subsets” (page unavailable), identifies multiple Prox1-expressing LEC clusters, including collecting LECs. But the Single-cell RNA-seq Methods (page unavailable) say the sequenced cells were isolated from mouse mesentery, not inguinal-axillary collecting vessels. The cited passages do not establish the claimed PDGFRα+ fibroblast-like, Myh11+ LMC, or multiple immune-cell clusters. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe single-cell transcriptome of LECs sorted from murine mesentery reveals an LEC population with 5-6 subclusters segregating into capillary LECs, precollecting/collecting vessel LECs, valve LECs, proliferative LECs, and IFN-responsive LECs, each with characteristic gene profile.
“The single-cell transcriptome of LECs sorted from murine mesentery reveals an LEC population with 5–6 subclusters segregating into capillary LECs, precollecting/collecting vessel LECs, valve LECs, proliferative LECs, and interferon (IFN)-responsive LECs, each with their own characteristic gene profile (15).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [15]
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β-Arrestin1/2 are essential for embryonic lymphatic vessel development
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Gelatinous drop-like amyloid in FOXC2 distichiasis syndrome: a case report
Sexton, G., Oury, N. H., Tripi, K. S., Nischal, K. K., & Chu, C. T. (2026) · BMC Ophthalmology · doi:10.1186/s12886-026-04800-1
Development and Function of Ovarian Lymphatic VasculaturePreprint
Biswas, S., Chen, L., Skalka, J., Xia, L., Srinivasan, R. S., Stout, M. B., & Geng, X. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.26.727976
Langerhans cell control of early-life dermal lymphatic development shapes adult immunity
Sim, J. H., Bell, R. D., Chinenov, Y. V., Feng, Z., Shin, J., Chyou, S., Shipman, W. D., Xing, Y., Naik, S., Anandasabapathy, N., et al. (2026) · Science Immunology · doi:10.1126/sciimmunol.aed8745
Lymphatic Endothelial Cells in Health and Disease
Tang, D., Wang, L., Liu, H., Zhong, J., Li, S., & Rao, X. (2026) · MedComm · doi:10.1002/mco2.70891
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Revisiting the role of lymphatics in Crohn’s disease
Berre, C. L., Ardabili, A. R., Czepielewski, R. S., Cices, A. D., Mehandru, S., & Jean-Frédéric, C. (2026) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izag187
- Authors
- González-Loyola, A., Bovay, E., Kim, J., Lozano, T. W., Sabine, A., Renevey, F., Arroz-Madeira, S., Rapin, A., Wypych, T. P., Rota, G., Durot, S., Velin, D., Marsland, B., Guarda, G., Delorenzi, M., Zamboni, N., Luther, S. A., & Petrova, T. V.
- Affiliations
- Department of Oncology, University of Lausanne and Ludwig Institute for Cancer Research Lausanne, Epalinges 1066, Switzerland.
- Ludwig Cancer Research (CH)
- Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
- École Polytechnique Fédérale de Lausanne (CH)
- Monash University (AU)
- University of Lausanne (CH)
- ETH Zurich (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Institute for Research in Biomedicine (CH)
- SIB Swiss Institute of Bioinformatics (CH)
- Corresponding author
- Petrova, Tatiana V.
- ORCID
- Venue
- Science Advances
- Published
- 2021-07-16
- Volume
- 7
- Issue
- 29
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC8284898
- OpenAlex
- W3182128200
- Cited by
- 94
- References
- 82
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 19 · 2023: 18 · 2022: 14 · 2021: 5
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by-nc)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion, cc-by-nc)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc)
- ETH Zürich Research Collection
- Funders
- Seventh Framework Programme (FP7/2007-2013_317250)
- Human Frontier Science Program (LT000074/2019-L, LT000633/2020-L)
- Swiss National Science Foundation (CRSII5_177191, 31ER30_160674, 31003A-156266, CRSK-3_190200, CRSII5, 31ER30, 190200, 310030, 185185, 310030_185226/1)
- Université de Lausanne (LT000074/2019-L)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- FOXC2, lymphatic endothelial cells, commensal microbiota, multiple organ failure, single-cell atlas, inflammatory bowel disease, lymphedema
- MeSH terms
- Endothelium, Lymphatic, Humans, Lymphedema, Lymphatic Vessels, Endothelial Cells, Forkhead Transcription Factors
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