Nature communicationsJun 17, 2026

A matched stem cell collection for studying Parkinson's disease

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 18, 2026

Abstract

An isogenic collection of 65 genome-edited human pluripotent stem cell lines has been established to study Parkinson's disease.

The collection includes lines carrying disease-causing or high-risk variants in 11 genes linked to Parkinson's disease.
Genetic variation among the lines is minimal compared to the variability found in patient-derived stem cells.
Most genetic differences arise from random mutations during cell culture rather than from unintended changes due to genome editing.
Using multiple independently derived clones for each mutation helps control for random genetic drift.
The approach highlights the benefits of prime editing over traditional CRISPR/Cas9 techniques.

Simplified

Genome-edited human pluripotent stem cells (hPSCs) provide a powerful platform to study complex diseases such as Parkinson's disease (PD). Here, we describe iSCORE-PD, an isogenic collection of 65 genome-edited hPSC lines carrying disease-causing or high-risk variants in 11 PD-linked genes (SNCA, PRKN, PINK1, DJ1/PARK7, LRRK2, ATP13A2, FBXO7, DNAJC6, SYNJ1, VPS13C, and GBA1). All lines are derived from a well-characterized female hESC line and subjected to extensive quality control. Whole-genome sequencing reveals that genetic variation between lines, largely confined to non-coding regions, is minimal relative to inter-individual differences in patient-derived hiPSCs, with most variation arising from random mutations acquired during cell culture rather than genome-editing-induced off-target effects. Including multiple independently derived clones per mutation can control for this random genetic drift. Our systematic approach ensures high quality of this publicly available iSCORE-PD resource, highlights the advantages of prime editing over conventional CRISPR/Cas9 methods, and establishes best practices for generating disease-modeling hPSC collections.