| Title: | iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease |
| Journal: | Nature Communications |
| Published: | 17 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42310027/ |
| DOI: | https://doi.org/10.1038/s41467-026-74355-8 |
Publication 20604
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Abstract
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.</p>
28 Authors
- Oriol Busquets
- Hanqin Li
- Khaja Mohieddin Syed
- Pilar Alvarez Jerez
- Jesse Dunnack
- Riana Lo Bu
- Yogendra Verma
- Gabriella R. Pangilinan
- Annika Martin
- Jannes Straub
- YuXin Du
- Vivien M. Simon
- Steven Poser
- Zipporiah Bush
- Jessica Diaz
- Atehsa Sahagun
- Jianpu Gao
- Samantha Hong
- Dena G. Hernandez
- Kristin S. Levine
- Nathalie Pochet
- Ezgi O. Booth
- Marco Blanchette
- Helen S. Bateup
- Donald C. Rio
- Cornelis Blauwendraat
- Dirk Hockemeyer
- Frank Soldner
1 Application
| Application ID | Title |
|---|---|
| 33601 | Dissecting the genetic architecture of neurodegenerative diseases |
Enabling scientific discoveries that improve human health