Browsing by Author "Zou, Yuhua"

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    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 Medicine
    Adult 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.
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    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 Medicine
    Although 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.