Institute of Cell Biology, ZMBE, Von-Esmarch-Straße 56, 48149 Muenster, Germany.
Institute of Human Genetics, Universitaetsklinikum Muenster, Vesaliusweg 12-14, 48149 Muenster, Germany.
Dev Cell. 2017 Dec 18;43(6):704-715.e5. doi: 10.1016/j.devcel.2017.11.019.
Maintaining cell fate relies on robust mechanisms that prevent the differentiation of specified cells into other cell types. This is especially critical during embryogenesis, when extensive cell proliferation, patterning, and migration events take place. Here we show that vertebrate primordial germ cells (PGCs) are protected from reprogramming into other cell types by the RNA-binding protein Dead end (Dnd). PGCs knocked down for Dnd lose their characteristic morphology and adopt various somatic cell fates. Concomitantly, they gain a gene expression profile reflecting differentiation into cells of different germ layers, in a process that we could direct by expression of specific cell-fate determinants. Importantly, we visualized these events within live zebrafish embryos, which provide temporal information regarding cell reprogramming. Our results shed light on the mechanisms controlling germ cell fate maintenance and are relevant for the formation of teratoma, a tumor class composed of cells from more than one germ layer.
维持细胞命运依赖于强大的机制,该机制可防止特定细胞分化为其他细胞类型。这在胚胎发生过程中尤为关键,在此期间,会发生广泛的细胞增殖、形态发生和迁移事件。在这里,我们表明脊椎动物原始生殖细胞(PGC)受到 RNA 结合蛋白 Dead end(Dnd)的保护,不会被重编程为其他细胞类型。Dnd 敲低的 PGC 失去其特征形态并采用各种体细胞命运。同时,它们获得了反映分化为不同胚层细胞的基因表达谱,我们可以通过表达特定的细胞命运决定因素来指导该过程。重要的是,我们在活体斑马鱼胚胎中可视化了这些事件,这些事件提供了有关细胞重编程的时间信息。我们的研究结果阐明了控制生殖细胞命运维持的机制,并且与畸胎瘤的形成有关,畸胎瘤是一种由一个以上胚层的细胞组成的肿瘤类别。