Single-Cell Profiling of Epigenetic Modifiers Identifies PRDM14 as an Inducer of Cell Fate in the Mammalian Embryo
Single-Cell Profiling of Epigenetic Modifiers Identifies PRDM14 as an Inducer of Cell Fate in the Mammalian Embryo
复制标题
DOI：
10.1016/j.celrep.2013.09.044
复制
发表时间：
2013-11-01
期刊：
影响因子：
8.8
通讯作者：
Torres-Padilla, Maria-Elena
中科院分区：
文献类型：
--
作者：
Burton, Adam;Muller, Julius;Torres-Padilla, Maria-Elena
细胞的可塑性或潜能对于多种细胞类型的形成是必要的。这种可塑性的机制在很大程度上是未知的。植入前小鼠胚胎经历细胞潜能的急剧变化，从全能合子开始，直到囊胚中多能性内细胞团（ICM）和分化的滋养外胚层的形成。在这里，我们着手确定和功能特性的染色质修饰剂，定义的效力和细胞命运的小鼠胚胎的过渡。在单细胞中使用定量微流体方法，我们表明，发育转变的标志是由表观遗传修饰剂的独特组合配置文件。ICM的多能细胞不同于其分化的滋养外胚层对应物。我们发现PRDM 14在4细胞期胚胎中不均匀表达。PRDM 14在2-细胞阶段的强制表达导致H3 R26 me 2增加，并且可以诱导多能ICM命运。我们的研究结果揭示了在体内支配细胞潜能和身份的表观遗传网络。
Cell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent inner cell mass (ICM) and differentiated trophectoderm in the blastocyst. Here, we set out to identify and functionally characterize chromatin modifiers that define the transitions of potency and cell fate in the mouse embryo. Using a quantitative microfluidics approach in single cells, we show that developmental transitions are marked by distinctive combinatorial profiles of epigenetic modifiers. Pluripotent cells of the ICM are distinct from their differentiated trophectoderm counterparts. We show that PRDM14 is heterogeneously expressed in 4-cell-stage embryos. Forced expression of PRDM14 at the 2-cell stage leads to increased H3R26me2 and can induce a pluripotent ICM fate. Our results shed light on the epigenetic networks that govern cellular potency and identity in vivo.