Examining iPSC derived motor neuron variability and genome stability monitoring as a solution.

ABSTRACT: Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) offer a promising model system for understanding motor neuron diseases (MNDs) and advancing drug discovery. However, variability in differentiation outcomes presents a major barrier to reproducibility and model reliability. This study evaluates a widely adopted small molecule protocol for MN differentiation to quantify variability and identify its sources within an industrial setting. Analysing data from 15 differentiation sets across 8 cell lines, we found that non-genetic factors - particularly induction set and operator - were the predominant sources of variability, outweighing the contribution from cell line genetics. We further demonstrated that iPSC genomic instability, as assessed by a targeted RT-qPCR assay for common

SUBMITTER: Gaffey F 

PROVIDER: S-EPMC12612198 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature