Generation of Neural Organoids for Spinal-Cord Regeneration via the Direct Reprogramming of Human Astrocytes
Authors
Jinhong Xu, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Shi Fang, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Suixin Deng, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Huijuan Li, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Xiaoning Lin, Department of Neurosurgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China.
Yongheng Huang, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Sangmi Chung, Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA.Follow
Yousheng Shu, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China.
Zhicheng Shao, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai, China. zcshao@fudan.edu.cn.
DOI
10.1038/s41551-022-00963-6
Journal Title
Nature Biomedical Engineering
Publication Date
3-1-2023
Department
Cell Biology and Anatomy
Abstract
Organoids with region-specific architecture could facilitate the repair of injuries of the central nervous system. Here we show that human astrocytes can be directly reprogrammed into early neuroectodermal cells via the overexpression of OCT4, the suppression of p53 and the provision of the small molecules CHIR99021, SB431542, RepSox and Y27632. We also report that the activation of signalling mediated by fibroblast growth factor, sonic hedgehog and bone morphogenetic protein 4 in the reprogrammed cells induces them to form spinal-cord organoids with functional neurons specific to the dorsal and ventral domains. In mice with complete spinal-cord injury, organoids transplanted into the lesion differentiated into spinal-cord neurons, which migrated and formed synapses with host neurons. The direct reprogramming of human astrocytes into neurons may pave the way for in vivo neural organogenesis from endogenous astrocytes for the repair of injuries to the central nervous system.
Recommended Citation
Xu, J., Fang, S., Deng, S., Li, H., Lin, X., Huang, Y., Chung, S., Shu, Y., & Shao, Z.
(2023). Generation of Neural Organoids for Spinal-Cord Regeneration via the Direct Reprogramming of Human Astrocytes. Nature Biomedical Engineering, 7 (3), 253-269.
https://doi.org/10.1038/s41551-022-00963-6
