Programmes of gene expression and mechanical property changes in mammalian one-cell embryos

The genome of gametes, sperm and oocyte, are silent, but in newly formed embryos,
transcription is activated via a process termed embryonic genome activation (EGA). EGA is a critical developmental event, yet its timing and profile remain elusive in both human and mouse. Our recent studies using high resolution single-cell RNA sequencing (scRNAseq) following polyadenylation-independent library preparation revealed that EGA initiates almost immediately after fertilisation, in one-cell stage human and mouse embryos (Asami et al., 2022 & 2023). We were interested in how this related to the physical properties of newly formed embryos: as with all cells, they comprise mechanically active matter that governs their functionality, but intracellular mechanics are difficult to study directly and are poorly understood. However, the large size of onecell mouse embryos (~100μm in diameter) combined with recent biophysical advances have presented new opportunities for us to assess their intracellular mechanobiology.
We identified a program of forces and changes to the cytoplasmic mechanical properties
required for the embryonic development from fertilisation to the first cell division (Duch
et al., 2020). In an initial effort to relate this to gene regulation, bioinformatics identified
experimentally verified upstream regulators commonly shared with cancer cells,
including c-Myc (Asami et al., 2022 & 2023, Perry et al., 2022). Together, these findings
shed light on the fundamental involvement of programmed mechanobiological and
transcriptional changes during the establishments of totipotency and open new windows
to understanding the initiation of cancer.