Neural Transcription Factor Research Articles

Steroid Anaesthesia

<h3>Abstract</h3> Glioblastoma (GBM) is the most prevalent and aggressive adult primary cancer in the central nervous system (CNS). Therapeutic approaches for glioblastoma are under intense investigation, such as the emerging immunotherapy, but so far only marginal progress has been made due to the heterogeneity and highly invasive nature of glioblastoma. Here, we propose an alternative approach to tackle GBM through reprogramming proliferative GBM cells into non-proliferative neurons. We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1 (NeuroD1), Neurogenin-2 (Neurog2) or Achaete-scute homolog 1 (Ascl1). Subtype characterization reveals that the majority of Neurog2- and NeuroD1-converted neurons are glutamatergic, while Ascl1 favors GABAergic neuron generation. The GBM cell-converted neurons not only express pan-neuronal markers, such as NeuN and MAP2, but also exhibit neuron-specific electrophysiological activities. We further conducted transcriptome analyses to investigate the underlying cell conversion mechanism. Our RNA-seq analyses discover that neuronal genes are activated among glioma cells after overexpression of neural transcription factors, and different signaling pathways are activated by different neural transcription factors. Importantly, the neuronal conversion of GBM cells is accompanied by significant inhibition of GBM cell proliferation in both <i>in vitro</i> and <i>in vivo</i> models. Therefore, these results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumor. <h3>Significance</h3> Converting dividing glioblastoma cells into non-dividing neurons may provide an innovative therapeutic approach to treat glioblastoma. <h3>Highlights</h3> Efficient neuronal conversion of human glioblastoma cells achieved by overexpression of neural transcription factors Neurog2- and NeuroD1-converted neurons are mostly glutamatergic, while Ascl1-converted neurons are mainly GABAergic Transcriptome analyses reveal the activation of neuronal genes after overexpression of neural transcription factors in glioblastoma cells Inhibition of cell proliferation during glioblastoma cell conversion both <i>in vitro</i> and <i>in vivo</i>