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. Overall design: Interrogation via single cell RNA and open chromatin sequencing experiments of cells isolated from the mouse central nervous system