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Browsing by Author "Zhang, Chun-Li"
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Item In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury(Cell Press, 2021) Tai, Wenjiao; Wu, Wei; Wang, Lei-Lei; Ni, Haoqi; Chen, Chunhai; Yang, Jianjing; Zang, Tong; Zou, Yuhua; Xu, Xiao-Ming; Zhang, Chun-Li; Neurological Surgery, School of MedicineAdult neurogenesis plays critical roles in maintaining brain homeostasis and responding to neurogenic insults. However, the adult mammalian spinal cord lacks an intrinsic capacity for neurogenesis. Here we show that spinal cord injury (SCI) unveils a latent neurogenic potential of NG2+ glial cells, which can be exploited to produce new neurons and promote functional recovery after SCI. Although endogenous SOX2 is required for SCI-induced transient reprogramming, ectopic SOX2 expression is necessary and sufficient to unleash the full neurogenic potential of NG2 glia. Ectopic SOX2-induced neurogenesis proceeds through an expandable ASCL1+ progenitor stage and generates excitatory and inhibitory propriospinal neurons, which make synaptic connections with ascending and descending spinal pathways. Importantly, SOX2-mediated reprogramming of NG2 glia reduces glial scarring and promotes functional recovery after SCI. These results reveal a latent neurogenic potential of somatic glial cells, which can be leveraged for regenerative medicine.Item NG2 Glia Reprogramming Induces Robust Axonal Regeneration After Spinal Cord Injury(bioRxiv, 2023-06-15) Tai, Wenjiao; Du, Xiaolong; Chen, Chen; Xu, Xiao-Ming; Zhang, Chun-Li; Wu, Wei; Neurological Surgery, School of MedicineSpinal cord injury (SCI) often leads to neuronal loss, axonal degeneration and behavioral dysfunction. We recently show that in vivo reprogramming of NG2 glia produces new neurons, reduces glial scaring, and ultimately leads to improved function after SCI. By examining endogenous neurons, we here unexpectedly uncover that NG2 glia reprogramming also induces robust axonal regeneration of the corticospinal tract and serotonergic neurons. Such reprogramming-induced axonal regeneration may contribute to the reconstruction of neural networks essential for behavioral recovery.Item NG2 glia reprogramming induces robust axonal regeneration after spinal cord injury(Elsevier, 2024-01-12) Tai, Wenjiao; Du, Xiaolong; Chen, Chen; Xu, Xiao-Ming; Zhang, Chun-Li; Wu, Wei; Neurological Surgery, School of MedicineSpinal cord injury (SCI) often leads to neuronal loss, axonal degeneration, and behavioral dysfunction. We recently show that in vivo reprogramming of NG2 glia produces new neurons, reduces glial scaring, and ultimately leads to improved function after SCI. By examining endogenous neurons, we here unexpectedly uncover that NG2 glia reprogramming also induces robust axonal regeneration of the corticospinal tract and serotonergic neurons. Such reprogramming-induced axonal regeneration may contribute to the reconstruction of neural networks essential for behavioral recovery.Item The p53 Pathway Controls SOX2-Mediated Reprogramming in the Adult Mouse Spinal Cord(Elsevier, 2016-10-11) Wang, Lei-Lei; Su, Zhida; Tai, Wenjiao; Zou, Yuhua; Xu, Xiao-Ming; Zhang, Chun-Li; Department of Neurological Surgery, IU School of MedicineAlthough the adult mammalian spinal cord lacks intrinsic neurogenic capacity, glial cells can be reprogrammed in vivo to generate neurons after spinal cord injury (SCI). How this reprogramming process is molecularly regulated, however, is not clear. Through a series of in vivo screens, we show here that the p53-dependent pathway constitutes a critical checkpoint for SOX2-mediated reprogramming of resident glial cells in the adult mouse spinal cord. While it has no effect on the reprogramming efficiency, the p53 pathway promotes cell-cycle exit of SOX2-induced adult neuroblasts (iANBs). As such, silencing of either p53 or p21 markedly boosts the overall production of iANBs. A neurotrophic milieu supported by BDNF and NOG can robustly enhance maturation of these iANBs into diverse but predominantly glutamatergic neurons. Together, these findings have uncovered critical molecular and cellular checkpoints that may be manipulated to boost neuron regeneration after SCI.Item Regeneration Through in vivo Cell Fate Reprogramming for Neural Repair(Frontiers Media, 2020-04-24) Tai, Wenjiao; Xu, Xiao-Ming; Zhang, Chun-Li; Neurological Surgery, School of MedicineThe adult mammalian central nervous system (CNS) has very limited regenerative capacity upon neural injuries or under degenerative conditions. In recent years, however, significant progress has been made on in vivo cell fate reprogramming for neural regeneration. Resident glial cells can be reprogrammed into neuronal progenitors and mature neurons in the CNS of adult mammals. In this review article, we briefly summarize the current knowledge on innate adult neurogenesis under pathological conditions and then focus on induced neurogenesis through cell fate reprogramming. We discuss how the reprogramming process can be regulated and raise critical issues requiring careful considerations to move the field forward. With emerging evidence, we envision that fate reprogramming-based regenerative medicine will have a great potential for treating neurological conditions such as brain injury, spinal cord injury (SCI), Alzheimer's disease (AD), Parkinson's disease (PD), and retinopathy.