iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.
iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
US · Author affiliation · country only
Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY, USA.Location evidence
Berkeley, US · Author affiliation
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.Location evidence
Bethesda, US · Author affiliation
Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.Location evidence
London, GB · Author affiliation
Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.Location evidence
Santa Cruz, US · Author affiliation
LiftOff Biosolution, Santa Cruz, CA, USA.Location evidence
San Francisco, US · Author affiliation
Chan Zuckerberg Biohub, San Francisco, CA, USA.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original 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.