Nickel exposure disrupts epigenetic repression of developmental genes in mouse embryonic stem cells

Examination of the underlying mechanisms revealed that Ni exposure induced a loss of the repressive histone modification H3K27me3 at bivalent mesodermal gene promoters, without altering its global levels. Pharmacological inhibition of H3K27me3 demethylases attenuated Ni-induced gene activation, confirming that H3K27me3 loss contributes to this process. ESCs are known to naturally exist as heterogeneous populations that fluctuate between naïve and lineage-primed pluripotent states.

Maintaining this balance is essential for proper differentiation. Our findings suggest that Ni exposure disrupts this equilibrium by prematurely inducing mesodermal and endodermal programs. Such dysregulation of early pluripotent states may bias cell-fate decisions and contribute to Ni-induced developmental toxicity, providing a mechanistic link between Ni exposure and developmental toxicity.