Alterations in chromatin organization promote totipotent-like features in a DPPA2/DUX-dependent manner.

Depleting WAPL and CTCF in mouse ESC promotes 2CLC reprogramming through chromatin organization changes, dependent on the DPPA2/DUX pathway, with a 2.5-fold increase observed.

• Why it matters: Understanding how chromatin structure influences totipotent-like states can reveal mechanisms of early development and reprogramming, addressing gaps in knowledge about chromatin's role in cell potency.
• What they did: The study used single-cell RNA-seq and ATAC-seq analyses on mouse ESC with WAPL and CTCF depletion, identifying chromatin accessibility as a precursor to 2C gene activation and implicating ARID3A as a regulator.
• The result: Findings demonstrate that chromatin organization alterations induce 2CLC features via the DPPA2/DUX axis, linking higher-order chromatin dynamics to totipotency-like cell identity and suggesting potential targets for reprogramming strategies.