cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels
cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels
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DOI：
10.1016/j.celrep.2015.02.026
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发表时间：
2015-03-17
期刊：
影响因子：
8.8
通讯作者：
Makinen, Taija
中科院分区：
文献类型：
--
作者：
Stanczuk, Lukas;Martinez-Corral, Ines;Makinen, Taija
病理性淋巴疾病主要影响特定组织中的血管，但对淋巴血管系统的器官特异性调节知之甚少。在此，我们发现血管内皮生长因子受体3(VEGFR-3)/p110αPI3-激酶信号通路选择性地参与肠系膜淋巴管的形成。利用遗传谱系追踪，我们证明了部分肠系膜淋巴管通过我们定义为淋巴管生成的过程从起源于血液内皮细胞的cKit谱系细胞发育而来。这与当前的教条相反，即所有哺乳动物的淋巴管都是从静脉中萌发形成的。我们的结果揭示了血管形成的起源和机制在血管床上的特异性差异，这可能是疾病中淋巴功能障碍的器官特异性表现的关键。在这项研究中确定的祖细胞可能被利用来恢复癌症手术、淋巴水肿或组织创伤后的淋巴功能。
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.