Neuronal differentiation of neuroblastoma cell lines for neurological disease modeling

Neurological disorders are often associated with neuronal dysfunction. Neuroblastoma (NB) cell line SH-SY5Y is widely used as in vitro model as it can differentiate into neuron-like cells. Many other NB cell lines can also respond to differentiation treatment but their potential in neuronal modeling remained unexplored. We evaluated 18 NB cell lines using RNA-seq and differentiation treatment with retinoic acid and brain-derived neurotrophic factor. Only few mutations in neurotransmitter pathway genes were detected. Transcription factor activities and differentially expressed genes classified NB cell lines into adrenergic (ADRN) and mesenchymal (MES) types. Each ADRN-type cell line exhibited a unique expression profile of neurotransmitter pathway genes. Differentiation treatment of ADRN-type cell lines CHP-134, LAN-5, and SIMA resulted in neuron-like cells expressing synaptic marker and several neurotransmitter pathway genes. Our results revealed ADRN-type cell lines can be selected carefully based on molecular background, differentiation potential and neuronal gene expression for neurological disease modeling.