Human neuroblastoma cell-derived neurons and iPSC-derived neurons as models for neuromuscular disorders

Haicui Wang, Claudia Pommerenke, Vivian Hauer, Ufert Rand, Sonja Eberth, Stefan Nagel, Wilhelm G.Dirks, Lisa Werr, Matthias Fischer & Laura Steenpass

The neuroblastoma (NB) cell lines such as SH-SY5Y have been widely used as in vitro neuron model. However, it also raised concerns as the cell lines are derived from malignant tumours. To provide a general guide on neuron model selection, we made a systematical characterization of 18 NB cell lines from our cell bank. Using RNA-seq, we identified key disease-causing mutations associated with neuroblastoma and additional mutations which might impact on mature neuron functions. The NB cell lines were grouped into adrenergic (ADRN) and mesenchymal (MES) types based on gene expression profiling and their response to retinoic acid (RA). The mature neurons derived from ADRN NB cell lines showed expression of common neuronal markers such as class III β-tubulin, neurofilaments, and preferential expression of genes for neuron subtypes such as TH gene for dopaminergic neurons. In summary, our comprehensive study demonstrated that the type of NB cell line, its tumour-associated mutations and individual gene expression pattern represent key factors for the selection of a suitable neuron model for neurodegenerative and neuromuscular studies. Furthermore, the NB neuron models promise low morphology variability and enable high throughput application.