In vivo reprogramming of NG2 glia enables adult neurogenesis and functional recovery following spinal cord injury

Wenjiao Tai, Wei Wu, Lei Lei Wang, Haoqi Ni, Chunhai Chen, Jianjing Yang, Tong Zang, Yuhua Zou, Xiao Ming Xu, Chun Li Zhang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)923-937.e4
JournalCell Stem Cell
Volume28
Issue number5
DOIs
StatePublished - May 6 2021

Keywords

  • NG2 glia
  • SOX2
  • adult neurogenesis
  • astrocytes
  • ependymal cells
  • glial scar
  • in vivo reprogramming
  • lineage tracing
  • monosynaptic connections
  • spinal cord injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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