STELLA and MuERV-L activation are essential for early mouse development. STELLA and MuERV-L activation are essential for early mouse development

The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. Here we investigated the function of the maternally inherited factor STELLA (DPPA3) using single-cell/embryo approaches. This submission concerns itself with transcriptional profiling of wild type and Stella knockout (Stella-/-) oocytes, wild type and Stella maternal/zygotic knockout (StellaM/Z-/-) 1-cell and 2-cell embryos. We show that loss of maternal STELLA results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of the LTR class of transposable elements (TE), and particularly 2-cell specific MuERV-L elements, is significantly impaired in StellaM/Z-/- embryos, which leads to a failure to upregulate selected chimeric transcripts. We propose that STELLA is involved in ensuring activation of TEs that themselves play a key role during early development, in part through regulating embryonic gene expression.

母源到合子转变（maternal-to-zygotic transition, MZT）标志着胚胎基因组激活并获得发育主控权的阶段。母源遗传因子在这一关键发育进程中发挥核心作用，该进程在小鼠中发生于2细胞期。本研究采用单细胞/胚胎研究方法，探究了母源遗传因子STELLA（DPPA3）的功能。本数据集涵盖野生型与Stella基因敲除（Stella-/-）卵母细胞、野生型及母源/合子源Stella敲除（StellaM/Z-/-）的1细胞与2细胞胚胎的转录谱分析。研究表明，母源STELLA的缺失会引发广泛的转录失调，并导致MZT部分失败。值得关注的是，长末端重复序列（Long Terminal Repeat, LTR）类转座因子（transposable elements, TE）的激活，尤其是2细胞特异性MuERV-L元件的激活，在StellaM/Z-/-胚胎中显著受损，进而无法上调特定嵌合转录本。我们提出，STELLA参与保障转座因子的激活，而这类转座因子本身在早期发育中发挥关键作用，其部分机制是通过调控胚胎基因表达实现的。