2. Academic Validation
  3. NeuroD4 converts glioblastoma cells into neuron-like cells through the SLC7A11-GSH-GPX4 antioxidant axis

NeuroD4 converts glioblastoma cells into neuron-like cells through the SLC7A11-GSH-GPX4 antioxidant axis

  • Cell Death Discov. 2023 Aug 15;9(1):297. doi: 10.1038/s41420-023-01595-8.
Hao Wang 1 2,  Peiqi Zhao 1 2,  Ying Zhang 1 2,  Zhen Chen 1 2,  Han Bao 1 2,  Wenqi Qian 1 2,  Jian Wu 1 2,  Zhenqiu Xing 1 2,  Xiaowei Hu 1 2,  Kunlin Jin 3,  Qichuan Zhuge 4 5,  Jianjing Yang 6 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
  • 4 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. qc.zhuge@wmu.edu.cn.
  • 5 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. qc.zhuge@wmu.edu.cn.
  • 6 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. yangjianjing@wmu.edu.cn.
  • 7 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. yangjianjing@wmu.edu.cn.
PMID: 37582760 DOI: 10.1038/s41420-023-01595-8
Abstract

Cell fate and proliferation ability can be transformed through reprogramming technology. Reprogramming glioblastoma cells into neuron-like cells holds great promise for glioblastoma treatment, as it induces their terminal differentiation. NeuroD4 (Neuronal Differentiation 4) is a crucial transcription factor in neuronal development and has the potential to convert astrocytes into functional neurons. In this study, we exclusively employed NeuroD4 to reprogram glioblastoma cells into neuron-like cells. In vivo, the reprogrammed glioblastoma cells demonstrated terminal differentiation, inhibited proliferation, and exited the cell cycle. Additionally, NeuroD4 virus-infected xenografts exhibited smaller sizes compared to the GFP group, and tumor-bearing mice in the GFP+NeuroD4 group experienced prolonged survival. Mechanistically, NeuroD4 overexpression significantly reduced the expression of SLC7A11 and Glutathione Peroxidase 4 (GPX4). The Ferroptosis inhibitor ferrostatin-1 effectively blocked the NeuroD4-mediated process of neuron reprogramming in glioblastoma. To summarize, our study demonstrates that NeuroD4 overexpression can reprogram glioblastoma cells into neuron-like cells through the SLC7A11-GSH-GPX4 signaling pathway, thus offering a potential novel therapeutic approach for glioblastoma.

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