Oct4 kinetics predict cell lineage patterning in the early mammalian embryo
Oct4 kinetics predict cell lineage patterning in the early mammalian embryo
复制标题
DOI：
10.1038/ncb2154
复制
发表时间：
2011-02-01
影响因子：
21.3
通讯作者：
Pantazis, Periklis
中科院分区：
文献类型：
--
作者：
Plachta, Nicolas;Bollenbach, Tobias;Pantazis, Periklis
转录因子是维持多能性的核心，但在早期哺乳动物胚胎中定义多能性的转录因子动力学知之甚少。在这里，我们建立了一个荧光衰减后光活化（FDAP）测定定量研究的动力学行为的Oct4，一个关键的转录因子控制小鼠胚胎植入前的发展。FDAP测量结果显示，发育中的胚胎中的每个细胞都显示出两种不同的Oct4动力学之一，在此之前，没有任何形态学上可区分的差异或谱系模式的外在迹象。FDAP所揭示的差异是由于Oct4与其在细胞核中的DNA结合位点的可及性差异。在两个不同的亚群中的细胞的谱系追踪表明，Oct4动力学预测早期胚胎的谱系。具有较慢Oct4动力学的细胞更可能产生有助于内细胞团的多能细胞谱系。那些具有更快的Oct4动力学的人主要贡献于胚胎外谱系。我们的研究结果确定了Oct4动力学，而不是总转录因子表达水平的差异，作为早期小鼠胚胎发育细胞谱系模式的预测指标。
Transcription factors are central to sustaining pluripotency, yet little is known about transcription factor dynamics in defining pluripotency in the early mammalian embryo. Here, we establish a fluorescence decay after photoactivation (FDAP) assay to quantitatively study the kinetic behaviour of Oct4, a key transcription factor controlling pre-implantation development in the mouse embryo. FDAP measurements reveal that each cell in a developing embryo shows one of two distinct Oct4 kinetics, before there are any morphologically distinguishable differences or outward signs of lineage patterning. The differences revealed by FDAP are due to differences in the accessibility of Oct4 to its DNA binding sites in the nucleus. Lineage tracing of the cells in the two distinct sub-populations demonstrates that the Oct4 kinetics predict lineages of the early embryo. Cells with slower Oct4 kinetics are more likely to give rise to the pluripotent cell lineage that contributes to the inner cell mass. Those with faster Oct4 kinetics contribute mostly to the extra-embryonic lineage. Our findings identify Oct4 kinetics, rather than differences in total transcription factor expression levels, as a predictive measure of developmental cell lineage patterning in the early mouse embryo.