Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway
Stem cell-derived endothelial cells/progenitors migrate and pattern in the embryo using the VEGF signaling pathway
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DOI：
10.1016/s0012-1606(03)00042-3
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发表时间：
2003-05-01
影响因子：
2.7
通讯作者：
Bautch, VL
中科院分区：
文献类型：
--
作者：
Ambler, CA;Schmunk, GM;Bautch, VL
内皮前体细胞响应分子信号迁移和组装成胚胎血管，但参与血管构型的信号通路还不是很清楚。我们最近通过对小鼠-鸟类嵌合体的分析表明，来自体细胞中胚层的哺乳动物血管母细胞可以识别鸟类的血管图案线索。为了确定干细胞来源的内皮细胞/前体细胞是否也识别全局模式信号，将小鼠ES细胞来源的类胚体(EBS)移植到禽类宿主体内。ES细胞来源的小鼠内皮细胞/前体细胞广泛迁移并在适当的宿主血管床上定植。它们还与禽类内皮细胞形成马赛克血管。与体细胞来源的内皮细胞不同，ES细胞来源的内皮细胞/祖细胞跨越宿主胚胎中线迁移到对侧。为了确定血管内皮生长因子信号在胚胎血管构型中的作用，将血管内皮生长因子受体突变体(Flk-1(-/-))或信号突变体(血管内皮生长因子-A(-/-))嫁接到宿主体内。Flk-1(-/-)EB移植只产生罕见的内皮细胞，不迁移或组装成血管。相比之下，血管内皮生长因子-A(-/-)EB移植产生的内皮细胞类似于野生型和定植的宿主血管床，这表明宿主来源的信号可以部分挽救突变的移植物血管模式。血管内皮生长因子-A(-/-)移植血管内皮细胞/祖细胞跨越宿主中线的频率比野生型EB移植物低得多，表明移植物来源的血管内皮生长因子在存在时损害了中线屏障。因此，ES细胞来源的内皮细胞/前体细胞对全球血管模式提示做出适当的反应，它们需要血管内皮生长因子信号通路来模式属性。此外，EB-禽类嵌合体提供了一种有效的方法来筛选血管图案缺陷的突变。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Endothelial precursor cells respond to molecular cues to migrate and assemble into embryonic blood vessels, but the signaling pathways involved in vascular patterning are not well understood. We recently showed that avian vascular patterning cues are recognized by mammalian angioblasts derived from somitic mesoderm through analysis of mouse-avian chimeras. To determine whether stem cell-derived endothelial cells/progenitors also recognize global patterning signals, murine ES cell-derived embryoid bodies (EBs) were grafted into avian hosts. ES cell-derived murine endothelial cells/progenitors migrated extensively and colonized the appropriate host vascular beds. They also formed mosaic vessels with avian endothelial cells. Unlike somite derived-endothelial cells, ES cell-derived endothelial cells/progenitors migrated across the host embryonic midline to the contralateral side. To determine the role of VEGF signaling in embryonic vascular patterning, EBs mutant for a VEGF receptor (flk-1(-/-)) or a signal (VEGF-A(-/-)) were grafted into quail hosts. Flk-1(-/-) EB grafts produced only rare endothelial cells that did not migrate or assemble into vessels. In contrast, VEGF-A(-/-) EB grafts produced endothelial cells that resembled wild-type and colonized host vascular beds, suggesting that host-derived signals can partially rescue mutant graft vascular patterning. VEGF-A(-/-) graft endothelial cells/progenitors crossed the host midline with much lower frequency than wild-type EB grafts, indicating that graft-derived VEGF compromised the midline barrier when present. Thus, ES cell-derived endothelial cells/progenitors respond appropriately to global vascular patterning cues, and they require the VEGF signaling pathway to pattern property. Moreover, EB-avian chimeras provide an efficient way to screen mutations for vascular patterning defects. (C) 2003 Elsevier Science (USA). All rights reserved.