State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, 100049 Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; College of Life Science, Northeast Agricultural University, 150030 Harbin, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
Cell. 2018 Dec 13;175(7):1887-1901.e18. doi: 10.1016/j.cell.2018.11.039.
In early mammalian embryos, it remains unclear how the first cell fate bias is initially triggered and amplified toward cell fate segregation. Here, we report that a long noncoding RNA, LincGET, is transiently and asymmetrically expressed in the nucleus of two- to four-cell mouse embryos. Overexpression of LincGET in one of the two-cell blastomeres biases its progeny predominantly toward the inner cell mass (ICM) fate. Mechanistically, LincGET physically binds to CARM1 and promotes the nuclear localization of CARM1, which can further increase the level of H3 methylation at Arginine 26 (H3R26me), activate ICM-specific gene expression, upregulate transposons, and increase global chromatin accessibility. Simultaneous overexpression of LincGET and depletion of Carm1 no longer biased embryonic fate, indicating that the effect of LincGET in directing ICM lineage depends on CARM1. Thus, our data identify LincGET as one of the earliest known lineage regulators to bias cell fate in mammalian 2-cell embryos.
在早期哺乳动物胚胎中，第一个细胞命运偏向最初是如何被触发并朝着细胞命运分离方向放大的，目前仍不清楚。在这里，我们报告称，一种长链非编码 RNA（LincGET）在两到四细胞期小鼠胚胎的细胞核中短暂且不对称地表达。在两个细胞胚泡中的一个中过表达 LincGET，使其后代主要偏向于内细胞团（ICM）命运。从机制上讲，LincGET 与 CARM1 物理结合，并促进 CARM1 的核定位，这可以进一步增加精氨酸 26 处的 H3 甲基化水平（H3R26me），激活 ICM 特异性基因表达，上调转座子，并增加全局染色质可及性。同时过表达 LincGET 和耗尽 Carm1 不再偏向胚胎命运，表明 LincGET 在指导 ICM 谱系中的作用依赖于 CARM1。因此，我们的数据确定 LincGET 是最早已知的在哺乳动物 2 细胞胚胎中偏向细胞命运的谱系调节因子之一。
