Senior Scientist, Postdoc Institute of Cytology, Russian Academy of Sciences (RAS), Saint Petersburg City, Russia
Abstract: Mammalian embryogenesis from fertilization to implantation represents a series of cleavages without significant embryo growth. The connection established between the embryo and the uterus after implantation in turn provides the necessary nutrients for further development and extensive growth of the body. This process also implies drastic metabolic changes in the cells of the epiblast, which undergo transition from naïve to primed pluripotency. Previously, embryos lacking the poly(rC)-DNA/RNA-binding protein Pcbp1 have been shown to exhibit a peri-implantation lethal phenotype, but the mechanisms underlying this phenotype are still unknown. In our study, using the multi-omics assays RNA-seq, ChIP-seq, shotgun proteomics, and metabolomics, we show that Pcbp1 is dispensable for the characteristics of naïve and primed pluripotency, but is crucial for the intensification of amino acid metabolism during the transition between the two states. Naïve embryonic stem cells deficient for Pcbp1 are viable, but their priming results in failed upregulation of genes related to amino acid uptake, serine/proline biosynthesis, and tRNA charging. As a result, the level of several amino acids decreases and protein synthesis declines, causing proliferation slowdown and apoptosis. In vivo, this phenotype manifests itself in a severe reduction in size and subsequent death of the embryos within a few days after implantation. In conclusion, our study describes a key role of Pcbp1 in early embryogenesis and helps to understand the anabolic mechanisms that enable substantial embryo growth after implantation.
Funding Source: The study was supported by the Russian Science Foundation (RSF) grant № 23-75-10096, https://rscf.ru/en/project/23-75-10096/.
