Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord

التفاصيل البيبلوغرافية
العنوان: Neurog2 directly converts astrocytes into functional neurons in midbrain and spinal cord
المؤلفون: 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
المصدر: Cell Death and Disease, Vol 12, Iss 3, Pp 1-16 (2021)
Cell Death & Disease
بيانات النشر: Nature Publishing Group, 2021.
سنة النشر: 2021
مصطلحات موضوعية: 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
الوصف: 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.
اللغة: English
تدمد: 2041-4889
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99cd4880e2470e137ba17ec70488208e
https://doaj.org/article/78db388ee70f49c9ad99132ff9bf6933
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....99cd4880e2470e137ba17ec70488208e
قاعدة البيانات: OpenAIRE