Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury
Summary: The transcriptome analysis of injured Xenopus laevis tadpole and mice suggested that Neurod4L.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 retro...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221000420 |
| _version_ | 1818416424580808704 |
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| author | Toshiki Fukuoka Akira Kato Masaki Hirano Fumiharu Ohka Kosuke Aoki Takayuki Awaya Alimu Adilijiang Maeda Sachi Kuniaki Tanahashi Junya Yamaguchi Kazuya Motomura Hiroyuki Shimizu Yoshitaka Nagashima Ryo Ando Toshihiko Wakabayashi Dasfne Lee-Liu Juan Larrain Yusuke Nishimura Atsushi Natsume |
| author_facet | Toshiki Fukuoka Akira Kato Masaki Hirano Fumiharu Ohka Kosuke Aoki Takayuki Awaya Alimu Adilijiang Maeda Sachi Kuniaki Tanahashi Junya Yamaguchi Kazuya Motomura Hiroyuki Shimizu Yoshitaka Nagashima Ryo Ando Toshihiko Wakabayashi Dasfne Lee-Liu Juan Larrain Yusuke Nishimura Atsushi Natsume |
| author_sort | Toshiki Fukuoka |
| collection | DOAJ |
| description | Summary: The transcriptome analysis of injured Xenopus laevis tadpole and mice suggested that Neurod4L.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 murine Neurod4 to mice undergoing SCI. SCI induced ependymal cells to neural stem cells (NSCs) in the central canal. The LCMV envelope-based pseudotypedvector preferentially introduced Neurod4 into 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, and Neurod4-induced excitatory neurons predominantly projected to subsynaptic domains of motor neurons caudal to the injury site suggesting the formation of functional synapses. Thus, Neurod4 is a potential therapeutic factor that can improve anatomical and functional recovery after SCI. |
| first_indexed | 2024-12-14T11:50:40Z |
| format | Article |
| id | doaj.art-6cd8182708364d5086ad0510d3d4d533 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-14T11:50:40Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6cd8182708364d5086ad0510d3d4d5332022-12-21T23:02:20ZengElsevieriScience2589-00422021-02-01242102074Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injuryToshiki Fukuoka0Akira Kato1Masaki Hirano2Fumiharu Ohka3Kosuke Aoki4Takayuki Awaya5Alimu Adilijiang6Maeda Sachi7Kuniaki Tanahashi8Junya Yamaguchi9Kazuya Motomura10Hiroyuki Shimizu11Yoshitaka Nagashima12Ryo Ando13Toshihiko Wakabayashi14Dasfne Lee-Liu15Juan Larrain16Yusuke Nishimura17Atsushi Natsume18Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, JapanGeroscience Center for Brain Health and Metabolism, Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, ChileCell and Molecular Biology, Developmental Biology and Regeneration, P. Universidad Catolica de Chile, Santiago, ChileDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan; Corresponding authorDepartment of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan; Corresponding authorSummary: The transcriptome analysis of injured Xenopus laevis tadpole and mice suggested that Neurod4L.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 murine Neurod4 to mice undergoing SCI. SCI induced ependymal cells to neural stem cells (NSCs) in the central canal. The LCMV envelope-based pseudotypedvector preferentially introduced Neurod4 into 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, and Neurod4-induced excitatory neurons predominantly projected to subsynaptic domains of motor neurons caudal to the injury site suggesting the formation of functional synapses. Thus, Neurod4 is a potential therapeutic factor that can improve anatomical and functional recovery after SCI.http://www.sciencedirect.com/science/article/pii/S2589004221000420Biological SciencesNeuroscienceBehavioral NeuroscienceCellular Neuroscience |
| spellingShingle | Toshiki Fukuoka Akira Kato Masaki Hirano Fumiharu Ohka Kosuke Aoki Takayuki Awaya Alimu Adilijiang Maeda Sachi Kuniaki Tanahashi Junya Yamaguchi Kazuya Motomura Hiroyuki Shimizu Yoshitaka Nagashima Ryo Ando Toshihiko Wakabayashi Dasfne Lee-Liu Juan Larrain Yusuke Nishimura Atsushi Natsume Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury iScience Biological Sciences Neuroscience Behavioral Neuroscience Cellular Neuroscience |
| title | Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| title_full | Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| title_fullStr | Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| title_full_unstemmed | Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| title_short | Neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| title_sort | neurod4 converts endogenous neural stem cells to neurons with synaptic formation after spinal cord injury |
| topic | Biological Sciences Neuroscience Behavioral Neuroscience Cellular Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221000420 |
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