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Lookup NU author(s): Antony Rose, Dr Simone WebbORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/Lymphatic vessels perform diverse functions, ranging from fluid homeostasis to immune regulation, and arise from multiple cellular origins to form organ-specific networks. Despite their importance in kidney disease and transplant immunity, the origins of kidney lymphatics are unknown. Using genetic lineage tracing in mice, we identify two origins of kidney lymphatics. Most kidney lymphatics arise from a Tie2+ endothelial origin shared by other organs. However, Osr1+ mesoderm generates approximately 15% of kidney lymphatics, without contributing to heart, mesentery, and skin lymphatics. Interrogating single-cell transcriptomics data of mice and humans reveals lymphatic progenitors within Osr1+ mesoderm. Lymphatic clusters forming by de novo assembly originate from both Osr1+ and Tie2+ lineages. Deleting the lymphatic specification gene Prox1 in Osr1+ mesoderm reduces lymphatic cluster number, impairing overall lymphatic network complexity, with lower glomerular number. Thus, an Osr1+ mesodermal origin contributes to organ-specific lymphatic assembly, with consequences for kidney health, disease, and regeneration.
Author(s): Jafree DJ, Russell LG, Stathopoulou A, O'Riordan C, Rowan CJ, White AT, Kolatsi-Joannou M, Price KL, Ivins S, Ridge LA, Roberts C, Rose A, Webb S, Vijayabaskar MS, Chandler JC, Wilson L, Pomeranz G, Moulding D, Davis B, Mitchell H, Siegenthaler J, Haniffa M, Woolf AS, Riley PR, Ruhrberg C, Scambler PJ, Rosenblum ND, Long DA
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2026
Pages: epub ahead of print
Online publication date: 19/06/2026
Acceptance date: 28/05/2026
Date deposited: 21/07/2026
ISSN (print): 2639-1856
ISSN (electronic): 2211-1247
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.celrep.2026.117560
DOI: 10.1016/j.celrep.2026.117560
Data Access Statement: All imaging files are available from the lead contact upon reasonable request. Previously published mouse single-nucleus transcriptomic data are deposited at the NCBI Gene Expression Omnibus and are publicly available.69 Previously published human single-cell/nucleus data, with additional new single-cell RNA sequencing (scRNA-seq) experiments of 5–6 PCW embryos, will be deposited in the EMBL-EBI ArrayExpress and made publicly available upon publication of the cited Human Developmental Cell Atlas (HDCA) manuscript from which the data is sourced.75 Accession numbers are listed in the key resources table. • All code used to analyze scRNA-seq data will be made available upon publication of the HDCA manuscript.75 • An interactive browser for mouse single-nucleus data is available at: https://omg.gs.washington.edu. HDCA data will be browsable using the following web portal: https://cellatlas.io/studies/hdca/.
PubMed id: 42320472
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