Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord
Hyukmin Kim,
Andy Skuba,
Jingsheng Xia,
Sung Baek Han,
Jinbin Zhai,
Huijuan Hu,
Shin H. Kang,
Young-Jin Son
Affiliations
Hyukmin Kim
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Andy Skuba
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Jingsheng Xia
Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ, USA
Sung Baek Han
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Jinbin Zhai
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Huijuan Hu
Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ, USA
Shin H. Kang
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Young-Jin Son
Department of Neural Sciences, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Corresponding author
Summary: Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:peripheral nervous system (PNS) borderline where OPCs are absent. Most axons stop in contact with a dense network of OPC processes. Live imaging, immuno-electron microscopy (immuno-EM), and OPC-dorsal root ganglia (DRG) co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.
