The neuroblastoma (NB) cell lines such as SH-SY5Y have been widely used as in vitro neuron model to evaluate mutation impact on neuron formation or morphology in many types of neuromuscular disorders. However, it also raised concerns as the cell lines are derived from malignant tumours. Meanwhile the induced pluripotent stem cell (iPSC)-derived neurons showed great potential in disease modelling due to the tumour-free background and more clinical relevance. To provide a general guide on neuron model selection for neuromuscular disorders (NMD), we made a systematical characterization of 17 NB cell lines from our cell bank, and also compared the NB-derived neurons with iPSC-derived neurons. 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 certain neuromuscular disorder related genes such as SLC5A7. On the other hand, the iPSC-derived neurons required longer and complicated differentiation process to achieve the mature neuron status. In summary, our comprehensive study demonstrated that the type of NB cell line, its tumour-associated mutations and individual NMD gene expression pattern represent key factors for the selection of a suitable NMD neuron model. Furthermore, the NB neuron models promise low morphology variability and enable high throughput application while the iPSC-derived neurons are more suitable for the validation of pathophysiological relevance.
Wang H., Pommerenke C., Hauer V., Rand U., Eberth S., Nagel S., Dirks W., Werr L., Fischer M. and Steenpaß L. Human neuroblastoma cell-derived and iPSC-derived neurons as models for neuromuscular disorders. 29th Annual Congress of the World Muscle Society, Prague, Czechia (08.-12.10.2024).
@misc{Wang2024,
Title = {Human neuroblastoma cell-derived and iPSC-derived neurons as models for neuromuscular disorders},
Author = {Wang, Haicui and Pommerenke, Claudia and Hauer, Vivien and Rand, Ulfert and Eberth, Sonja and Nagel, Stefan and Dirks, Wilhelm and Werr, Lisa and Fischer, Matthias and Steenpaß, Laura},
Editor = {},
Year = {2024},
Doi = {10.1016/j.nmd.2024.07.087},
Abstract = {The neuroblastoma (NB) cell lines such as SH-SY5Y have been widely used as in vitro neuron model to evaluate mutation impact on neuron formation or morphology in many types of neuromuscular disorders. However, it also raised concerns as the cell lines are derived from malignant tumours. Meanwhile the induced pluripotent stem cell (iPSC)-derived neurons showed great potential in disease modelling due to the tumour-free background and more clinical relevance. To provide a general guide on neuron model selection for neuromuscular disorders (NMD), we made a systematical characterization of 17 NB cell lines from our cell bank, and also compared the NB-derived neurons with iPSC-derived neurons. 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 certain neuromuscular disorder related genes such as SLC5A7. On the other hand, the iPSC-derived neurons required longer and complicated differentiation process to achieve the mature neuron status. In summary, our comprehensive study demonstrated that the type of NB cell line, its tumour-associated mutations and individual NMD gene expression pattern represent key factors for the selection of a suitable NMD neuron model. Furthermore, the NB neuron models promise low morphology variability and enable high throughput application while the iPSC-derived neurons are more suitable for the validation of pathophysiological relevance.},
}
TY - GEN
AU - Wang, Haicui
AU - Pommerenke, Claudia
AU - Hauer, Vivien
AU - Rand, Ulfert
AU - Eberth, Sonja
AU - Nagel, Stefan
AU - Dirks, Wilhelm
AU - Werr, Lisa
AU - Fischer, Matthias
AU - Steenpaß, Laura
TI - Human neuroblastoma cell-derived and iPSC-derived neurons as models for neuromuscular disorders
PY - 2024
DO - 10.1016/j.nmd.2024.07.087
AB - The neuroblastoma (NB) cell lines such as SH-SY5Y have been widely used as in vitro neuron model to evaluate mutation impact on neuron formation or morphology in many types of neuromuscular disorders. However, it also raised concerns as the cell lines are derived from malignant tumours. Meanwhile the induced pluripotent stem cell (iPSC)-derived neurons showed great potential in disease modelling due to the tumour-free background and more clinical relevance. To provide a general guide on neuron model selection for neuromuscular disorders (NMD), we made a systematical characterization of 17 NB cell lines from our cell bank, and also compared the NB-derived neurons with iPSC-derived neurons. 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 certain neuromuscular disorder related genes such as SLC5A7. On the other hand, the iPSC-derived neurons required longer and complicated differentiation process to achieve the mature neuron status. In summary, our comprehensive study demonstrated that the type of NB cell line, its tumour-associated mutations and individual NMD gene expression pattern represent key factors for the selection of a suitable NMD neuron model. Furthermore, the NB neuron models promise low morphology variability and enable high throughput application while the iPSC-derived neurons are more suitable for the validation of pathophysiological relevance.
CY - Prague, Czechia
ER -
