Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex  

作　　者：Zongqin Xiang Liang Xu Minhui Liu Qingsong Wang Wen Li Wenliang Lei Gong Chen 

机构地区：[1]Guangdong-Hong Kong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,Guangdong Province,China [2]Department of Neurosurgery,the First Affiliated Hospital,Jinan University,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2021年第4期750-756,共7页中国神经再生研究（英文版）

基　　金：This study was supported by the National Natural Science Foundation of China(No.U1801681,to GC and No.31970906,to WL);Guangdong Science and Technology Department(‘Key technologies for treatment of brain disorders’,No.2018B030332001,to GC);the Natural Science Foundation of Guangdong Province of China(No.2020A1515011079,to WL and No.2020A1515010854,to QW);the internal funding from Jinan University(No.21616110,to GC);the Young Scientists Fund of the National Natural Science Foundation of China(No.31701291,to WL).

摘　　要：Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018.

关 键 词：adeno-associated viruses ASTROCYTE dosage glia-to-neuron conversion in vivo reprogramming lineage tracing NEURON RETROVIRUS 

分 类 号：R459.9[医药卫生—治疗学] R364.3[医药卫生—临床医学]