Translational gene regulation in mouse gastruloids

Abstract

Mechanisms to regulate gene expression have been studied thoroughly throughout the years mostly on the transcriptional level. There have been examples though where the presence of translational control regulated important biological processes. In this project we investigated whether translational control plays an important role during early embryonic development. For that we used mouse embryonic stems cells and 120-hour mouse gastruloids that develop somites. The experiments were performed on a single cell level and two genome-wide sequencing methods were used to quantify transcription (scVASA-seq) and translation (scRibo-seq). With scVASA-seq, all types of RNA molecules were sequenced. With scRibo-seq, ribosomal footprints were created that capture actively translating ribosomes on mRNA molecules. From the analysis, cells from both techniques were integrated computationally, and eight different clusters of cell types were identified. The cell-type identities of these clusters were annotated based on marker gene expression. Changes in Translational Efficiency (ΔΤΕ) between clusters were calculated and compared. We identified 86 genes that undergo translational control that further clustered into three groups. An enrichment analysis for biological processes of the genes in these groups provided further information about the biological procedures these genes are involved in. This work conducted the first genome-wide measurements of translation and translation efficiency during mouse gastrulation, providing insight into the role post-transcriptional regulation plays in this important developmental process.