title: Evaluation of inter-batch differences in stem-cell derived neurons.
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.
authors.affiliation: Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Gladys
authors.initials: G
authors.lastname: Morrison
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wing
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Delaney
authors.affiliation: Department of Preventive Medicine & The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: wei.zhang1@northwestern.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL 60637, USA; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address: edolan@medicine.bsd.uchicago.edu.
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Dolan
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017239:Paclitaxel; D017423:Sequence Analysis, RNA; D059467:Transcriptome / Q000187:drug effects; D014750:Vincristine / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D017239:Paclitaxel; D002945:Cisplatin
keywords: Chemotherapy; Induced pluripotent stem cells; Neuron; Neuropathy