Replication stress primes a trophectoderm fate in embryonic stem cells

ABSTRACT: Early embryogenesis is marked by extremely rapid cell cycles that generate significant replication stress (RS), but how this stress influences cell-fate potential is not fully understood. Using mouse embryonic stem cells as a model of the inner cell mass, we show that RS quickly and persistently activates trophectoderm (TE) regulators. Quantitative chromatin proteomics reveals a characteristic RS-induced remodeling: nucleosomes and condensin are displaced, while DNA repair proteins and ATR cofactors become enriched on chromatin. This proteomic signature indicates a highly accessible, checkpoint-responsive chromatin state that enables lineage reprogramming. Together, these results define an ATR- and JNK/c-JUN-driven stress pathway that can shift embryonic cell identity toward TE and, when aberrantly re-engaged in adult cells, may promote maladaptive fate changes relevant to cancer development.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Giorgia Parodi  

LAB HEAD: Angela Bachi

PROVIDER: PXD071534 | Pride | 2026-09-07

REPOSITORIES: Pride