Evaluation of inter-batch differences in stem-cell derived neurons

Gladys Morrison, Cong Liu, Claudia Wing, Shannon M. Delaney, Wei Zhang*, M. Eileen Dolan

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Differentiated cells retain the genetic information of the donor but the extent to which phenotypic differences between donors or batches of differentiated cells are explained by variation introduced during the differentiation process is not fully understood. In this study, we evaluated four separate batches of commercially available neurons originating from the same iPSCs to investigate whether the differentiation process used in manufacturing iPSCs to neurons affected genome-wide gene expression and modified cytosines, or neuronal sensitivity to drugs. No significant changes in gene expression, as measured by RNA-Seq, or cytosine modification levels, as measured by the Illumina 450K arrays, were observed between batches relative to changes over time. As expected, neurotoxic chemotherapeutics affected neuronal outgrowth, but no inter-batch differences were observed in sensitivity to paclitaxel, vincristine and cisplatin. As a testament to the utility of the model for studies of neuropathy, we observed that genes involved in neuropathy had relatively higher expression levels in these samples across different time points. Our results suggest that the process used to differentiate iPSCs into neurons is consistent, resulting in minimal intra-individual variability across batches. Therefore, this model is reasonable for studies of human neuropathy, druggable targets to prevent neuropathy, and other neurological diseases.

Original languageEnglish (US)
Pages (from-to)140-148
Number of pages9
JournalStem Cell Research
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Chemotherapy
  • Induced pluripotent stem cells
  • Neuron
  • Neuropathy

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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  • Cite this

    Morrison, G., Liu, C., Wing, C., Delaney, S. M., Zhang, W., & Dolan, M. E. (2016). Evaluation of inter-batch differences in stem-cell derived neurons. Stem Cell Research, 16(1), 140-148. https://doi.org/10.1016/j.scr.2015.12.025