To accurately orchestrate distinct cell fates during early development, RNAs play a crucial role by being transported to the correct subcellular regions at the appropriate times, where they are then translated into functional proteins. However, the subcellular mechanisms for the efficient and timely directed transport of RNAs and their local translation remain less understood in mammalian embryogenesis. Here, using advanced microinjection and live imaging technologies, we observed RNA real-time dynamics and translation at different stages of mouse preimplantation embryos, regulating cell fate during the initial days of life.
At the 1-cell stage, we observed for the first time that RNA transcription occurs in the second polar body, which was previous regarded as a useless byproduct of embryonic development. A specific subset of mRNAs encoding pluripotency-related factors is enriched in the second polar body. Consequently, proteins are translated and transported from the second polar body to the embryo. This results in asymmetric allocation of pluripotency factors to the two blastomeres following the first cell division, leading to a bias in cell fate between the blastomeres at the 2-cell stage. The blastomere attached to the second polar body exhibits greater pluripotency compared to the other cell, contributing more descendants to the pluripotent inner cells from 16-cell stage. From this stage, pluripotent inner cells are segregated from differentiated outer cells through asymmetric divisions. During this process, we visualised the dynamics of global mRNA contents being transported to the apical region of the outer cells with higher translation activity, which prepares the outer cells to differentiate into trophectoderm.
Our study pioneered real-time imaging of RNA contents at different stages of early mammalian embryos to regulate cell fate, offering new insights into the dynamic nature of RNAs and translation activity during preimplantation embryogenesis, extending beyond the analysis of single gene transcripts.