A latent lineage potential in resident neural stem cells enables spinal cord repair
Enric Llorens-Bobadilla, James M. Chell, Pierre Le Merre, Yi‐Cheng Wu, Margherita Zamboni, Joseph Bergenstråhle, Moa Stenudd, Elena Sopova, Joakim Lundeberg, Oleg Shupliakov, Marie Carlén, Jonas Frisén
Abstract
Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multimodal single-cell analysis, we found that neural stem cells are in a permissive chromatin state that enables the unfolding of a normally latent gene expression program for oligodendrogenesis after injury. Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell-derived oligodendrogenesis, which followed the natural progression of oligodendrocyte differentiation, contributed to axon remyelination, and stimulated functional recovery of axon conduction. Recruitment of resident stem cells may thus serve as an alternative to cell transplantation after CNS injury.