1. Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord.
- Author
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Liu F, Zhang Y, Chen F, Yuan J, Li S, Han S, Lu D, Geng J, Rao Z, Sun L, Xu J, Shi Y, Wang X, and Liu Y
- Subjects
- Animals, Astrocytes ultrastructure, Basic Helix-Loop-Helix Transcription Factors genetics, Cells, Cultured, Dependovirus genetics, Gene Transfer Techniques, Genetic Vectors, Glutamate Decarboxylase genetics, Glutamate Decarboxylase metabolism, Mesencephalon ultrastructure, Mice, Transgenic, Nerve Tissue Proteins genetics, Neurons ultrastructure, Oxidoreductases Acting on CH-NH Group Donors genetics, Oxidoreductases Acting on CH-NH Group Donors metabolism, Phenotype, Spinal Cord ultrastructure, Vesicular Glutamate Transport Protein 2 genetics, Vesicular Glutamate Transport Protein 2 metabolism, Astrocytes metabolism, Basic Helix-Loop-Helix Transcription Factors metabolism, Cell Transdifferentiation, Mesencephalon metabolism, Nerve Tissue Proteins metabolism, Neurogenesis, Neurons metabolism, Spinal Cord metabolism
- Abstract
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.
- Published
- 2021
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