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Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects

Michael J. Workman, Ryan G. Lim, Jie Wu, Aaron P. Frank, Loren Ornelas, Lindsay Panther, Erick Galvez, Daniel I. Pérez, Imara Meepe, Susan Lei, Viviana Valencia, Emilda Gomez, Chunyan Liu, Ruby Moran, Louis Pinedo, Stanislav Tsitkov, Ritchie Ho, Julia Kaye, Terri G. Thompson, Jeffrey D. Rothstein, Steven Finkbeiner, Ernest Fraenkel, Dhruv Sareen, Leslie M. Thompson, Clive N. Svendsen

2023Neuron89 citationsDOIOpen Access PDF

Abstract

Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack of well-curated lines from a large array of participants. Answer ALS has generated over 1,000 iPSC lines from control and amyotrophic lateral sclerosis (ALS) patients along with clinical and whole-genome sequencing data. The current report summarizes cell marker and gene expression in motor neuron cultures derived from 92 healthy control and 341 ALS participants using a 32-day differentiation protocol. This is the largest set of iPSCs to be differentiated into motor neurons, and characterization suggests that cell composition and sex are significant sources of variability that need to be carefully controlled for in future studies. These data are reported as a resource for the scientific community that will utilize Answer ALS data for disease modeling using a wider array of omics being made available for these samples.

Topics & Concepts

NeurosciencePsychologyScale (ratio)BiologyCartographyGeographyAmyotrophic Lateral Sclerosis ResearchNeurological disorders and treatmentsNeurogenesis and neuroplasticity mechanisms