A latent lineage potential in resident neural stem cells

Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells exist, but manifest a very limited contribution to cell replacement. Here we uncover a latent potential in neural stem cells to replace large numbers of oligodendrocytes in the injured mouse spinal cord. Using single cell genomics 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. Once unveiled, stem cell-derived oligodendrogenesis is abundant, follows the natural progression of oligodendrocyte differentiation, contributes to axon remyelination and stimulates functional recovery of axon conduction. Resident stem cells can thus serve as a meaningful reservoir for cellular replacement and constitute an alternative to cell transplantation after CNS injury. Interrogation via single cell RNA and open chromatin sequencing experiments of cells isolated from the mouse central nervous system