Tracking and mitigating imprint erasure during induction of naive human pluripotency at single-cell resolution.

ABSTRACT: Naive human pluripotent stem cells (hPSCs) model the pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded in naive hPSCs, which represents an important deviation from the epiblast in vivo. To track the dynamics of imprint erasure during naive resetting in real time, we established a dual-colored fluorescent reporter at both alleles of the imprinted SNRPN locus. During primed-to-naive resetting, SNRPN expression becomes biallelic in most naive cells, and biallelic SNRPN expression is irreversible upon re-priming. We utilized this live-cell reporter to evaluate chemical and genetic strategies to minimize imprint erasure. Decreasing the level of MEK/ERK inhibition or overexpressing the KRAB zinc-finger protein ZFP57 protected a subset of imprints during n

SUBMITTER: Fischer LA 

PROVIDER: S-EPMC11960550 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature