Dissecting cell-intrinsic and extrinsic effects of DNA demethylation during gastrulation

The three TET enzymes actively demethylate DNA and mice deficient of the three enzymes die shortly after gastrulation. We revisited this mutant phenotype using temporal single-cell atlases from embryos with partial or complete mutant contributions. Strikingly, when developing within a wild-type embryo, Tet-mutant cells retain near-complete differentiation potential, whereas full-embryo mutants fail to generate ectoderm and most embryonic mesoderm lineages.