Passage number affects differentiation of sensory neurons from human induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to hetero...

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Bibliographic Details
Published inScientific reports Vol. 12; no. 1; pp. 1 - 9
Main Authors Cantor, Erica L., Shen, Fei, Jiang, Guanglong, Tan, Zhiyong, Cunningham, Geneva M., Wu, Xi, Philips, Santosh, Schneider, Bryan P.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 23.09.2022
Nature Publishing Group
Nature Portfolio
Subjects
631/1647/767/1658
631/532/1360
Cell culture
Genetics
Heterogeneity
Humanities and Social Sciences
Inhibitory postsynaptic potentials
Morphology
multidisciplinary
Neurogenesis
Neurological diseases
Neurons
Peripheral blood
Phenotypes
Pluripotency
Science
Science (multidisciplinary)
Sensory neurons
Stem cells
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Summary:Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to heterogeneity in culture conditions. We investigated the effect of passage number on iPSC differentiation to optimize the generation of sensory neurons (iPSC-dSNs). Three iPSC lines reprogrammed from the peripheral blood of three donors were differentiated into iPSC-dSNs at passage numbers within each of the following ranges: low (5–10), intermediate (20–26), and high (30–38). Morphology and pluripotency of the parent iPSCs were assessed prior to differentiation. iPSC-dSNs were evaluated based on electrophysiological properties and expression of key neuronal markers. All iPSC lines displayed similar morphology and were similarly pluripotent across passage numbers. However, the expression levels of neuronal markers and sodium channel function analyses indicated that iPSC-dSNs differentiated from low passage numbers better recapitulated the sensory neuron phenotype than those differentiated from intermediate or high passage numbers. Our results demonstrate that lower passage numbers may be better suited for differentiation into peripheral sensory neurons.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-19018-6