Establishment of four induced pluripotent stem cell lines with high polygenic risk score for Parkinson's disease.

Four induced pluripotent stem cell lines were established from dermal fibroblasts of early-onset sporadic Parkinson’s disease patients selected for high PD polygenic risk scores, enabling modeling of lysosomal and microglial genetic contributions.

• Why it matters: Sporadic PD has an estimated heritability of ∼ 25%, yet polygenic risk—especially in lysosomal and microglial pathways—needs patient-derived models to study.
• What they did: Dermal fibroblasts from four early-onset sporadic PD patients with high PD PRS were reprogrammed into iPSCs using Sendai virus, then assessed by karyotyping, STR matching to donor blood, pluripotency marker expression, and tri-lineage differentiation; lysosomal and microglial open chromatin PRSs were also calculated.
• The result: The resulting iPSC lines have normal karyotypes and donor-matched STR profiles and differentiate into all three germ layers, providing a resource to model polygenic, high-risk sporadic PD with focus on lysosomal and microglial genetics.

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