文章基本信息

标题：Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury
本地全文：下载
作者：Toshiki Fukuoka ; Akira Kato ; Masaki Hirano 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-47
DOI：10.1016/j.isci.2021.102074
语种：English
出版社：Elsevier
摘要：SummaryThe transcriptome analysis of injuredXenopus laevistadpole and mice suggested thatNeurod4L.S., a basic-helix-loop-helix transcription factor, was the most promising transcription factor to exert neuroregeneration after spinal cord injury (SCI) in mammals. We generated a pseudotyped retroviral vector with the neurotropic lymphocytic choriomeningitis virus (LCMV) envelope to deliver murineNeurod4to mice undergoing SCI. SCI induced ependymal cells to neural stem cells (NSCs) in the central canal. The LCMV envelope-based pseudotypedvector preferentially introducedNeurod4into activated NSCs, which converted to neurons with axonal regrowth and suppressed the scar-forming glial lineage.Neurod4-induced inhibitory neurons predominantly projected to the subsynaptic domains of motor neurons at the epicenter, andNeurod4-induced excitatory neurons predominantly projected to subsynaptic domains of motor neurons caudal to the injury site suggesting the formation of functional synapses. Thus,Neurod4is a potential therapeutic factor that can improve anatomical and functional recovery after SCI.Graphical abstractDisplay OmittedHighlights•Neurod4is predominantly expressed in injuredXenopus laevistadpole•An LCMV-based pseudotyped retroviral vector has tropism to neural stem cells•Neurod4converts endogenous neural stem cells to neurons after spinal cord injury•The new excitatory and inhibitory synaptic formation leads to functional recoveryBiological Sciences; Neuroscience; Behavioral Neuroscience; Cellular Neuroscience