Bcl- xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells

Yunqin Wu; Xiaohua Peng; Song Ang; Yue Gao; Yue Chi; Jinling Wang; Chengcheng Tang; Xiaoqing Zhou; Yanxian Feng; Kun Zhang; Qingjian Zou; Min Chen

doi:10.3390/biology12010132

Bcl- xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells

Biology (Basel). 2023 Jan 13;12(1):132. doi: 10.3390/biology12010132.

Authors

Yunqin Wu¹, Xiaohua Peng¹, Song Ang^{1

2}, Yue Gao¹, Yue Chi¹, Jinling Wang¹, Chengcheng Tang¹, Xiaoqing Zhou¹, Yanxian Feng¹, Kun Zhang^{1

2}, Qingjian Zou¹, Min Chen^{1

2}

Affiliations

¹ Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine, Wuyi University, Jiangmen 529020, China.
² International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China.

Abstract

Neural stem cell (NSC) transplantation creates new hope for the treatment of neurodegenerative disorders by direct differentiation into neurons. However, this technique is limited by poor survival and functional neuron deficiency. In this research study, we generated pro-survival murine NSCs (mNSCs) via the ectopic expression of Bcl-xL. A doxycycline (Dox)-inducible Ngn2-Isl1-Lhx3 system was also integrated into the mNSC genome. The four gene-modified mNSCs can rapidly and effectively differentiate into motor neurons after Dox treatments. Ectopic Bcl-xL could resist replating-induced stress, glutamate toxicity, neuronal apoptosis and remarkably promote the survival of motor neurons. Taken together, we established genetically modified mNSCs with improved survival, which may be useful for motor neuron degenerative diseases.

Keywords: Bcl-xL; motor neurons; neural stem cells; survival.

Grants and funding

The National Natural Science Foundation of China (No. 82001974); the Science and Technology Planning Project of Guangdong Province, China (No. 2021B1212040016); and the Open Fund of the CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine (No. 2020B1212060052).