Physiological pathway of differentiation of hematopoietic stem cell population into mural cells.
Physiological pathway of differentiation of hematopoietic stem cell population into mural cells.
复制标题
造血干细胞种群分化为壁细胞的生理途径。
DOI：
10.1084/jem.20050373
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发表时间：
2006-04-17
期刊：
影响因子：
--
通讯作者：
Takakura N
中科院分区：
文献类型：
--
作者：
Yamada Y;Takakura N
据报道，内皮细胞（EC）是血管的主要组成部分，在成年期由造血细胞群（尤其是单核细胞系的细胞群）发育而来。在这里，我们基于HSC的体外培养和缺乏HSC的急性髓系白血病1突变体胚胎的组织学检查，表明血管的另一种成分壁细胞（MC）在造血干细胞（HSC）群体的胚胎发生过程中进行生理发育。与胚胎中一样，成人骨髓中的 HSC 在分化为 MC 之前先分化为 CD45+CD11b+ 细胞。此外，CD45+CD11b+细胞由两个群体组成，CD11bhigh和CD11blow细胞，两者都可以分化为MC和EC。有趣的是，在小鼠缺血模型中，与 CD11high 群体相比，源自 CD11blow 群体的 MC 和 EC 具有长期促进体内新发育血管形成的潜力，而 CD11high 群体则不能。此外，注射CD11bhigh群体会引起血管渗漏，但CD11blow群体则不会。关于血管的通透性，我们发现血管生成素 1 是 EC 上表达的 Tie2 受体酪氨酸激酶的配体，被认为可以诱导 EC 和 MC 之间的细胞粘附，它是由 CD11blow 群体产生的，在非渗漏血管的形成中发挥着关键作用。这些观察结果表明 CD11low 细胞群是体内血管再生的良好细胞来源。
Endothelial cells (ECs), which are a major component of blood vessels, have been reported to develop in adulthood from hematopoietic cell populations, especially those of the monocyte lineage. Here we show that mural cells (MCs), another component of blood vessels, develop physiologically during embryogenesis from a hematopoietic stem cell (HSC) population, based on the in vitro culture of HSCs and histological examination of acute myeloid leukemia 1 mutant embryos, which lack HSCs. As in the embryo, HSCs in adult bone marrow differentiate into CD45+CD11b+ cells before differentiating into MCs. Moreover, CD45+CD11b+ cells are composed of two populations, CD11bhigh and CD11blow cells, both of which can differentiate into MCs as well as ECs. Interestingly, in a murine ischemia model, MCs and ECs derived from the CD11blow population had a long-term potential to contribute to the formation of newly developed blood vessels in vivo compared with the CD11high population, which could not. Moreover, injection of the CD11bhigh population induced leaky blood vessels, but the CD11blow population did not. With respect to the permeability of vessels, we found that angiopoietin 1, which is a ligand for Tie2 receptor tyrosine kinase expressed on ECs and is suggested to induce cell adhesion between ECs and MCs, is produced by the CD11blow population and plays a critical role in the formation of nonleaky vessels. These observations suggested that the CD11low cell population serves as a good source of cells for in vivo blood vessel regeneration.
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