Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells.
Proper migration of lymphatic endothelial cells requires survival and guidance cues from arterial mural cells.
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DOI：
10.7554/elife.74094
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发表时间：
2022-03-22
期刊：
影响因子：
7.7
通讯作者：
Koltowska, Katarzyna
中科院分区：
文献类型：
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作者：
Peng, Di;Ando, Koji;Hussmann, Melina;Gloger, Marleen;Skoczylas, Renae;Mochizuki, Naoki;Betsholtz, Christer;Fukuhara, Shigetomo;Schulte-Merker, Stefan;Lawson, Nathan D.;Koltowska, Katarzyna
淋巴内皮细胞（LECs）的迁移是复杂而庞大的淋巴血管网络发展的关键，渗透在生物体的大多数组织中。在斑马鱼中，动脉节间血管与趋化因子一起被证明可以促进淋巴细胞从水平肌隔（HM）迁移。我们观察到，壁细胞在节段间动脉周围的出现与淋巴离开HM的时间一致，这提出了动脉壁细胞促进LEC迁移的可能性。我们的实时成像和细胞消融实验显示，在没有动脉壁细胞的情况下，LECs迁移速度较慢，无法建立淋巴血管网络。我们确定壁细胞是C- x -C基序列趋化因子12 （Cxcl12a和Cxcl12b）、血管内皮生长因子C （Vegfc）以及胶原和钙结合EGF结构域蛋白1 （Ccbe1）的来源。我们发现趋化因子和生长因子信号传导共同作用，诱导LEC强劲迁移。具体来说，Vegfc-Vegfr3信号传导，而不是趋化因子，诱导LECs细胞外信号调节激酶（ERK）激活，并在LECs迁移过程中具有额外的促存活作用。总之，鉴定壁细胞作为指导LEC迁移和存活的信号来源，将对未来设计重建疾病背景下的淋巴管具有重要意义。
The migration of lymphatic endothelial cells (LECs) is key for the development of the complex and vast lymphatic vascular network that pervades most tissues in an organism. In zebrafish, arterial intersegmental vessels together with chemokines have been shown to promote lymphatic cell migration from the horizontal myoseptum (HM). We observed that emergence of mural cells around the intersegmental arteries coincides with lymphatic departure from HM which raised the possibility that arterial mural cells promote LEC migration. Our live imaging and cell ablation experiments revealed that LECs migrate slower and fail to establish the lymphatic vascular network in the absence of arterial mural cells. We determined that mural cells are a source for the C-X-C motif chemokine 12 (Cxcl12a and Cxcl12b), vascular endothelial growth factor C (Vegfc) and collagen and calcium-binding EGF domain-containing protein 1 (Ccbe1). We showed that chemokine and growth factor signalling function cooperatively to induce robust LEC migration. Specifically, Vegfc-Vegfr3 signalling, but not chemokines, induces extracellular signal-regulated kinase (ERK) activation in LECs, and has an additional pro-survival role in LECs during the migration. Together, the identification of mural cells as a source for signals that guide LEC migration and survival will be important in the future design for rebuilding lymphatic vessels in disease contexts.