Paper details
Latent regenerative potential in resident neural stem cells
1 Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
2 Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden
3 Science for Life Laboratory, Karolinska Institutet Science Park, SE-171 21 Solna, Sweden
4 Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia
5 Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83, Huddinge, Sweden
Abstract
Injuries to the mammalian central nervous system are inefficiently repaired. Resident neural stem cells exist, but manifest a limited contribution to cell replacement. Here we uncover a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multiple layers of genomic information in single cells we found that the genetic program for oligodendrogenesis is accessible in neural stem cells.
However, this programme remains latent after injury, as its critical regulators are not expressed, leading to inefficient oligodendrocyte replacement. We found that ectopic expression of Olig2 led to the activation of the latent program after injury, which was followed by abundant stem cell-derived oligodendrogenesis.
Oligodendrogenesis elicited from resident neural stem cells followed the developmental progression of oligodendrocyte differentiation, contributed to axon remyelination and stimulated functional recovery of axon conduction. Targeted activation of latent regenerative programs in non-regenerative tissues may thus be an effective strategy to enhance the repair.