Stem Cell Haematopoiesis Group, Cancer Research, UK.
Blood. 2010 May 13;115(19):3895-8. doi: 10.1182/blood-2009-10-247395. Epub 2010 Mar 12.
We have previously shown that Sox7 was transiently expressed at the onset of blood specification and was implicated in the regulation of cell survival, proliferation, and maturation of hematopoietic precursors. Here, we assessed, using embryonic stem cell differentiation as a model system, whether Sox17 and Sox18, 2 close homologs of Sox7, may act similarly to Sox7 at the onset of hematopoietic development. Sox18-enforced expression led to the enhanced proliferation of early hematopoietic precursors while blocking their maturation, phenotype highly reminiscent of Sox7-enforced expression. In striking contrast, Sox17-enforced expression dramatically increased the apoptosis of these early precursors. Similarly to Sox7, Sox18 was transiently expressed during early hematopoiesis, but its expression was predominantly observed in CD41(+) cells, contrasting with Sox7, mostly expressed in Flk1(+) cells. Conversely, Sox17 remained marginally expressed during blood specification. Overall, our data uncover contrasting effect and expression pattern for Sox18 and Sox17 at the onset of hematopoiesis specification.
我们之前已经表明，Sox7 在血液特化开始时短暂表达，并涉及造血前体细胞的细胞存活、增殖和成熟的调控。在这里，我们使用胚胎干细胞分化作为模型系统评估了 Sox17 和 Sox18，Sox7 的 2 个紧密同源物，是否可能在造血发育开始时与 Sox7 类似地发挥作用。Sox18 的强制表达导致早期造血前体的增殖增强，同时阻止其成熟，其表型高度类似于 Sox7 的强制表达。相比之下，Sox17 的强制表达显著增加了这些早期前体的细胞凋亡。与 Sox7 类似，Sox18 在早期造血过程中短暂表达，但主要在 CD41(+)细胞中观察到其表达，与 Sox7 主要在 Flk1(+)细胞中表达形成对比。相反，Sox17 在血液特化期间仍然呈边缘表达。总体而言，我们的数据揭示了 Sox18 和 Sox17 在造血特化开始时的相反作用和表达模式。
