Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord
Autor: | Dengyu Lu, Yuhan Shi, Xiaojing Wang, Yijie Zhang, Fei Liu, Li Sun, Fuliang Chen, Jianhua Xu, Liu Yueguang, Sanlan Li, Jiacheng Yuan, Zhiping Rao, Junlan Geng, Sue Han |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Cancer Research
Neurogenesis Genetic Vectors Immunology Mice Transgenic Nerve Tissue Proteins Biology Adult neurogenesis Article Midbrain Cellular and Molecular Neuroscience Glutamatergic Dorsal root ganglion Mesencephalon Basic Helix-Loop-Helix Transcription Factors medicine Biological neural network Animals lcsh:QH573-671 Cells Cultured Neurons Oxidoreductases Acting on CH-NH Group Donors Glutamate Decarboxylase lcsh:Cytology Gene Transfer Techniques Cell Biology Dependovirus Spinal cord Electrophysiology Phenotype medicine.anatomical_structure Spinal Cord nervous system Astrocytes Cell Transdifferentiation embryonic structures Vesicular Glutamate Transport Protein 2 Neuronal development Ectopic expression Neuroscience |
Zdroj: | Cell Death and Disease, Vol 12, Iss 3, Pp 1-16 (2021) Cell Death & Disease |
ISSN: | 2041-4889 |
Popis: | Conversion of astrocytes into neurons in vivo offers an alternative therapeutic approach for neuronal loss after injury or disease. However, not only the efficiency of the conversion of astrocytes into functional neurons by single Neurog2, but also the conundrum that whether Neurog2-induced neuronal cells (Neurog2-iNs) are further functionally integrated into existing matured neural circuits remains unknown. Here, we adopted the AAV(2/8) delivery system to overexpress single factor Neurog2 into astrocytes and found that the majority of astrocytes were successfully converted into neuronal cells in multiple brain regions, including the midbrain and spinal cord. In the midbrain, Neurog2-induced neuronal cells (Neurog2-iNs) exhibit neuronal morphology, mature electrophysiological properties, glutamatergic identity (about 60%), and synapse-like configuration local circuits. In the spinal cord, astrocytes from both the intact and lesioned sources could be converted into functional neurons with ectopic expression of Neurog2 alone. Notably, further evidence from our study also proves that Neurog2-iNs in the intact spinal cord are capable of responding to diverse afferent inputs from dorsal root ganglion (DRG). Together, this study does not merely demonstrate the feasibility of Neurog2 for efficient in vivo reprogramming, it gives an indication for the Neurog2-iNs as a functional and potential factor in cell-replacement therapy. |
Databáze: | OpenAIRE |
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