Modeling ATN1 mutations in human iPSCs reveals early developmental roles of atrophin-1

An isogenic human iPSC panel shows that ATN1 loss or mutant-only expression causes marked proliferation deficits and enhanced punctate ATN1 assemblies, with pluripotency markers unchanged.

• Why it matters: ATN1 is linked to neuronal development and severe disorders like DRPLA and CHEDDA, but its cellular roles in early human development are not well defined.
• What they did: The study built an isogenic iPSC panel (wt/mut, wt/wt, -/-, wt/-, and -/mut) using patient-derived lines and CRISPR-Cas9 correction, then assessed pluripotency, proliferation, and ATN1 assembly formation.
• The result: Proliferation deficits appear in ATN1 knock-out and heterozygous iPSCs lacking wild-type allele expression, while -/mut variants enhance punctate ATN1 assemblies, enabling mechanistic studies of ATN1-dependent neuronal development.

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