CKit lineage hemogenic endothelium-derived cells contribute to mesenteric lymphatic vessels

Lukas Stanczuk, Ines Martinez-Corral, Maria H. Ulvmar, Yang Zhang, Bàrbara Laviña, Marcus Fruttiger, Ralf H. Adams, Dieter Saur, Christer Betsholtz, Sagrario Ortega, Kari Alitalo, Mariona Graupera, Taija Mäkinen

Research output: Contribution to journalArticlepeer-review

188 Scopus citations

Abstract

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)/p110α 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.

Original languageEnglish
Pages (from-to)1708-1721
Number of pages14
JournalCell Reports
Volume10
Issue number10
DOIs
StatePublished - 17 Mar 2015

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