Differential neuronal reprogramming induced by NeuroD1 from astrocytes in grey matter versus white matter  

作　　者：Min-Hui Liu Wen Li Jia-Jun Zheng Yu-Ge Xu Qing He Gong Chen 

机构地区：[1]Guangdong-HongKong-Macao Institute of CNS Regeneration (GHMICR),Jinan University,Guangzhou,Guangdong Province,China [2]Department of Biology,The Huck Institutes of Life Sciences,The Pennsylvania State University,University Park,PA,USA

出　　处：《Neural Regeneration Research》2020年第2期342-351,共10页中国神经再生研究（英文版）

基　　金：supported in part by the National Natural Science Foundation of China(Grant No.31701291 to WL,U1801681 to GC);the China Postdoctoral Science Foundation(Grant No.2016M602600 to WL);the Guangdong Grant ‘Key Technologies for Treatment of Brain Disorders’(Grant No.2018B030332001 to GC);the Internal Funding of Jinan University,China(Grant No.21616110 to GC)

摘　　要：A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018.A new technology called in vivo glia-to-neuron conversion has emerged in recent years as a promising next generation therapy for neural regeneration and repair. This is achieved through reprogramming endogenous glial cells into neurons in the central nervous system through ectopically expressing neural transcriptional factors in glial cells. Previous studies have been focusing on glial cells in the grey matter such as the cortex and striatum, but whether glial cells in the white matter can be reprogrammed or not is unknown. To address this fundamental question, we express NeuroD1 in the astrocytes of both grey matter(cortex and striatum) and white matter(corpus callosum) to investigate the conversion efficiency, neuronal subtypes, and electrophysiological features of the converted neurons. We discover that NeuroD1 can efficiently reprogram the astrocytes in the grey matter into functional neurons, but the astrocytes in the white matter are much resistant to neuronal reprogramming. The converted neurons from cortical and striatal astrocytes are composed of both glutamatergic and GABAergic neurons, capable of firing action potentials and having spontaneous synaptic activities. In contrast, the few astrocyte-converted neurons in the white matter are rather immature with rare synaptic events. These results provide novel insights into the differential reprogramming capability between the astrocytes in the grey matter versus the white matter, and highlight the impact of regional astrocytes as well as microenvironment on the outcome of glia-toneuron conversion. Since human brain has large volume of white matter, this study will provide important guidance for future development of in vivo glia-to-neuron conversion technology into potential clinical therapies. Experimental protocols in this study were approved by the Laboratory Animal Ethics Committee of Jinan University(approval No. IACUC-20180321-03) on March 21, 2018.

关 键 词：ASTROCYTE CONVERSION efficiency corpus callosum cortex grey MATTER in vivo cell CONVERSION NeuroD1 neuron REPROGRAMMING STRIATUM white MATTER 

分 类 号：R446[医药卫生—诊断学] R364[医药卫生—临床医学]