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

• DOI: 10.1016/j.stemcr.2025.102419
• Publication Date: 2025-02-13T22:04:29Z
• Authors: Laura A. Fischer; Brittany Meyer; Monica Reyes; Joseph E. Zemke; Jessica K. Harrison; Kyoung-mi Park; Ting Wang; Harald Jüppner; Sabine Dietmann; Thorold W. Theuni...
• Keywords: Erasure; Single-Cell Analysis; Tracking (education)

Highlights•A biallelic, dual-colored fluorescent reporter at the imprinted SNRPN locus in hPSCs•Biallelic expression is rapidly induced during primed-to-naive resetting•Acquisition of biallelic irreversible upon re-priming•ZFP57 overexpression mitigates imprint erasure resettingSummaryNaive human pluripotent stem cells (hPSCs) model pre-implantation epiblast. However, parent-specific epigenetic marks (imprints) are eroded naive hPSCs, which represents an important deviation from epiblast vivo. To track dynamics resetting real time, we established a both alleles locus. During resetting, becomes most cells, and re-priming. We utilized this live-cell to evaluate chemical genetic strategies minimize erasure. Decreasing level MEK/ERK inhibition or overexpressing KRAB zinc-finger protein ZFP57 protected subset imprints resetting. Combining these two levels further extent than either strategy alone. This study offers experimental tool enhance stability transitions between states vitro.Graphical abstract