Department of Cell and Developmental Biology and Centre for Stem Cells and Regenerative Medicine, University College London, WC1E 6DE London, UK.
Dev Cell. 2013 Mar 25;24(6):586-99. doi: 10.1016/j.devcel.2013.01.022. Epub 2013 Mar 7.
Pericytes are endothelial-associated cells that contribute to vessel wall. Here, we report that pericytes may derive from direct conversion of committed skeletal myoblasts. When exposed to Dll4 and PDGF-BB, but not Dll1, skeletal myoblasts downregulate myogenic genes, except Myf5, and upregulate pericyte markers, whereas inhibition of Notch signaling restores myogenesis. Moreover, when cocultured with endothelial cells, skeletal myoblasts, previously treated with Dll4 and PDGF-BB, adopt a perithelial position stabilizing newly formed vessel-like networks in vitro and in vivo. In a transgenic mouse model in which cells expressing MyoD activate Notch, skeletal myogenesis is abolished and pericyte genes are activated. Even if overexpressed, Myf5 does not trigger myogenesis because Notch induces Id3, partially sequestering Myf5 and inhibiting MEF2 expression. Myf5-expressing cells adopt a perithelial position, as occasionally also observed in wild-type (WT) embryos. These data indicate that endothelium, via Dll4 and PDGF-BB, induces a fate switch in adjacent skeletal myoblasts.
周细胞是与血管内皮相关的细胞，有助于血管壁的形成。在这里，我们报告周细胞可能来源于定向分化的成肌细胞的直接转化。当成肌细胞暴露于 Dll4 和 PDGF-BB 时，除了 Myf5 外，成肌细胞下调肌生成基因并上调周细胞标志物，但抑制 Notch 信号通路可恢复肌生成。此外，当与内皮细胞共培养时，先前用 Dll4 和 PDGF-BB 处理的成肌细胞会获得周细胞的位置，在体外和体内稳定新形成的血管样网络。在一个转基因小鼠模型中，表达 MyoD 的细胞激活 Notch，导致成肌细胞消失和周细胞基因激活。即使过表达，Myf5 也不会触发肌生成，因为 Notch 诱导 Id3，部分隔离 Myf5 并抑制 MEF2 的表达。Myf5 表达的细胞获得周细胞的位置，这在野生型（WT）胚胎中偶尔也会观察到。这些数据表明，内皮细胞通过 Dll4 和 PDGF-BB 诱导相邻成肌细胞的命运转变。
