@article{a602469c40dd4b87b6bcf4cff46d7963,
title = "In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury",
abstract = "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.",
keywords = "NG2 glia, SOX2, adult neurogenesis, astrocytes, ependymal cells, glial scar, in vivo reprogramming, lineage tracing, monosynaptic connections, spinal cord injury",
author = "Wenjiao Tai and Wei Wu and Wang, {Lei Lei} and Haoqi Ni and Chunhai Chen and Jianjing Yang and Tong Zang and Yuhua Zou and Xu, {Xiao Ming} and Zhang, {Chun Li}",
note = "Funding Information: We thank members of the Zhang laboratory for discussions and reagents and J.E. Johnson (UT Southwestern, USA) for the ASCL1 antibody. C.-L.Z. is a W.W. Caruth, Jr. Scholar in Biomedical Research. The work in the Zhang laboratory was supported by the Welch Foundation ( I-1724 ), the Decherd Foundation , the Texas Alzheimer{\textquoteright}s Research and Care Consortium ( TARCC2020 ), the Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration , and the NIH ( NS099073 , NS092616 , NS111776 , NS117065 , and NS088095 ). The work in the Xu laboratory was supported by the NIH ( 1R01NS100531 , 1R01NS103481 , and 1R01NS111776 ) and Department of Veterans Affairs (1IK6 BX004204 ). Funding Information: We thank members of the Zhang laboratory for discussions and reagents and J.E. Johnson (UT Southwestern, USA) for the ASCL1 antibody. C.-L.Z. is a W.W. Caruth, Jr. Scholar in Biomedical Research. The work in the Zhang laboratory was supported by the Welch Foundation (I-1724), the Decherd Foundation, the Texas Alzheimer's Research and Care Consortium (TARCC2020), the Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, and the NIH (NS099073, NS092616, NS111776, NS117065, and NS088095). The work in the Xu laboratory was supported by the NIH (1R01NS100531, 1R01NS103481, and 1R01NS111776) and Department of Veterans Affairs (1IK6 BX004204). W.T. W.W. L.-L.W. X.-M.X. and C.-L.Z. conceived and designed the experiments. W.T. W.W. and L.-L.W. performed the experiments. H.N. C.C. J.Y. and T.Z. provided critical reagents and scientific inputs. Y.Z. maintained mouse colonies. W.T. W.W. L.-L.W. X.-M.X. and C.-L.Z. analyzed data. W.T. W.W. L.-L.W. and C.-L.Z. wrote the manuscript. All authors reviewed and approved the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = may,
day = "6",
doi = "10.1016/j.stem.2021.02.009",
language = "English (US)",
volume = "28",
pages = "923--937.e4",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}