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<p>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 (<i>SNCA, PRKN, PINK1, DJ1/PARK7, LRRK2, ATP13A2, FBXO7, DNAJC6, SYNJ1, VPS13C</i>, and <i>GBA1</i>). 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>

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iSCORE-PD: an isogenic stem cell collection to research Parkinson’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月17日

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  • 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

摘要

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.