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Development of a human iPSC and patient phenotyping resource for preclinical investigations of neurodevelopmental disorders.

Cidi Chen·Wardiya Afshar-Saber·Isabela Iglesias·Kristina Kim·Becca Lewis·Gayathri Srinivasan·Celeste Chen·Remi Hirsh·Ryan Guardado·Taryn Polanco·Amanda Swanson·Erika Norabuena·Dosh Whye·Ashish Jain·Chunhui Cai·Liang Sun·Maya Chopra·Ivy Chen·Grazia Iannello·Brian Rozumny·Ellen Hanson·Mustafa Sahin·Elizabeth D Buttermore
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Abstract

In this manuscript, we report the development of a comprehensive resource designed to harness the transformative potential of patient-derived induced pluripotent stem cells (iPSCs) to advance the study of neurodevelopmental disorders (NDDs). Using CRISPR-Cas-mediated genome editing, the Human Neuron Core generated a repository comprising 29 isogenic iPSC pairs, two sex-matched parental control iPSC pairs, and one unmatched patient line representing six monogenic NDDs: Tuberous Sclerosis Complex, PTEN Hamartoma Tumor Syndrome, KCNQ2 Developmental and Epileptic Encephalopathy, FOXG1 Syndrome, Phelan-McDermid Syndrome, and SETBP1 Haploinsufficiency Disorder. In parallel, detailed clinical phenotyping data were collected to enable comparison of cellular phenotypes with clinical severity in future studies. This integrated collection of genetically defined iPSC lines and associated clinical data provides a powerful platform for investigating disease mechanisms and advancing iPSC-based drug discovery for NDDs.

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HumansInduced Pluripotent Stem CellsNeurodevelopmental DisordersPhenotypeFemaleCRISPR-Cas SystemsMaleCRISPR-CAS9Gene editingHuman induced pluripotent stem cellsNeurodevelopmental disordersJournal Article

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Cidi Chen, Wardiya Afshar-Saber, Isabela Iglesias, Kristina Kim, Becca Lewis, Gayathri Srinivasan, Celeste Chen, Remi Hirsh, Ryan Guardado, Taryn Polanco, Amanda Swanson, Erika Norabuena, Dosh Whye, Ashish Jain, Chunhui Cai, Liang Sun, Maya Chopra, Ivy Chen, Grazia Iannello, Brian Rozumny, Ellen Hanson, Mustafa Sahin, Elizabeth D Buttermore. 2026-08-06. Development of a human iPSC and patient phenotyping resource for preclinical investigations of neurodevelopmental disorders.. https://doi.org/10.1016/j.scr.2026.104073

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