The question of what guides lineage segregation is central to development,
where cellular differentiation leads to segregated cell populations destined
for specialized functions. Here, using optical tweezers measurements of mouse
embryonic stem cells (mESCs), we reveal a mechanical mechanism based on
differential elasticity in the second lineage segregation of the embryonic
inner cell mass into epiblast (EPI) cells - that will develop into the fetus -
and primitive endoderm (PrE) - which will form extraembryonic structures such
as the yolk sac. Remarkably, we find that these mechanical differences already
occur during priming and not just after a cell has committed to
differentiation. Specifically, we show that the mESCs are highly elastic
compared to any other reported cell type and that the PrE cells are
significantly more elastic than EPI-primed cells. Using a model of two cell
types differing only in elasticity we show that differential elasticity alone
can lead to segregation between cell types, suggesting that the mechanical
attributes of the cells contribute to the segregation process. Our findings
present differential elasticity as a previously unknown mechanical contributor
to the lineage segregation during the embryo morphogenesis