Myeloid lineage progenitors give rise to vascular endothelium

Myeloid lineage progenitors give rise to vascular endothelium
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DOI:
10.1073/pnas.0604203103
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发表时间:
2006-08-29
影响因子:
11.1
通讯作者:
Fleming, William H.
Fleming, William H.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bailey, Alexis S.;Willenbring, Holger;Fleming, William H.

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尽管内皮祖细胞在血管发育和修复中发挥重要作用,但其起源仍然未知。越来越多的证据表明,源自造血系统的细胞参与血管生成。然而,这些细胞的身份和功能作用仍然存在争议。在这里,我们证明血管内皮细胞可以从常见的骨髓祖细胞和粒细胞/巨噬细胞祖细胞分化。源自移植骨髓源性骨髓谱系祖细胞的内皮细胞表达 CD31、冯·维勒布兰德因子和 Tie2,但不表达造血标记物 CD45 和 F4/80 或周细胞标记物结蛋白和平滑肌肌动蛋白。谱系追踪分析与 Tie2 驱动的 Cre/lox 报告系统相结合表明,与骨髓来源的肝细胞相比,骨髓来源的内皮细胞不是细胞融合的产物。联体共生后造血细胞和内皮细胞嵌合的建立表明,循环细胞可以在没有急性辐射损伤的情况下产生血管内皮。我们的研究结果表明,内皮细胞是骨髓谱系分化的内在组成部分,并强调了造血系统和血管系统之间的密切功能关系。
Despite an important role in vascular development and repair, the origin of endothelial progenitors remains unknown. Accumulating evidence indicates that cells derived from the hematopoietic system participate in angiogenesis. However, the identity and functional role of these cells remain controversial. Here we show that vascular endothelial cells can differentiate from common myeloid progenitors and granulocyte/macrophage progenitors. Endothelial cells derived from transplanted bone marrow-derived myeloid lineage progenitors expressed CD31, von Willebrand factor, and Tie2 but did not express the hematopoietic markers CD45 and F4/80 or the pericyte markers desmin and smooth muscle actin. Lineage tracing analysis in combination with a Tie2-driven Cre/lox reporter system revealed that, in contrast to bone marrow-derived hepatocytes, bone marrow-derived endothelial cells are not the products of cell fusion. The establishment of both hematopoietic and endothelial cell chimerism after parabiosis demonstrates that circulating cells can give rise to vascular endothelium in the absence of acute radiation injury. Our findings indicate that endothelial cells are an intrinsic component of myeloid lineage differentiation and underscore the close functional relationship between the hematopoietic and vascular systems.