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cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
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2015 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 10, no 10, 1708-1721 p.Article in journal (Refereed) Published
Abstract [en]

Pathological lymphatic diseases mostly affect vessels in specific tissues, yet little is known about organ-specific regulation of the lymphatic vasculature. Here, we show that the vascular endothelial growth factor receptor 3 (VEGFR-3)/p110 alpha PI3-kinase signaling pathway is selectively required for the formation of mesenteric lymphatic vasculature. Using genetic lineage tracing, we demonstrate that part of the mesenteric lymphatic vasculature develops from cKit lineage cells of hemogenic endothelial origin through a process we define as lymphvasculogenesis. This is contrary to the current dogma that all mammalian lymphatic vessels form by sprouting from veins. Our results reveal vascular-bed-specific differences in the origin and mechanisms of vessel formation, which may critically underlie organ-specific manifestation of lymphatic dysfunction in disease. The progenitor cells identified in this study may be exploited to restore lymphatic function following cancer surgery, lymphedema, or tissue trauma.

Place, publisher, year, edition, pages
2015. Vol. 10, no 10, 1708-1721 p.
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Cell and Molecular Biology
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URN: urn:nbn:se:uu:diva-251417DOI: 10.1016/j.celrep.2015.02.026ISI: 000351316700008OAI: oai:DiVA.org:uu-251417DiVA: diva2:807436
Available from: 2015-04-23 Created: 2015-04-17 Last updated: 2017-12-04Bibliographically approved

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Martinez-Corral, InesUlvmar, Maria H.Zhang, YangLaviña, BàrbaraBetsholtz, ChristerMäkinen, Taija

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