Spinal stem cells in mice can be reprogrammed to generate protective oligodendrocytes after spinal cord injury, enhancing neural repair, according to a new study. It reveals the latent transcriptional potential of mouse ependymal cells in findings that suggest that recruitment of resident stem cells through similar means may serve as an alternative to stem cell transplantation after central nervous system injury. "To realize the potential of ependymal cell in human spinal cord injuries, it will be necessary to determine whether similar stem cells exist near the human spinal cord central canal in sufficient numbers," write Catherina Becker and Thomas Becker in a related Perspective. In mammals, spinal cord damage destroys key cells, including oligodendrocytes, which provide the protective insulation surrounding neural "wiring." While resident stem cells, like ependymal cells, are present in the brain and spinal cord, they have a propensity to produce scar tissue instead of the replacement cells needed to repair damage after injury. Finding a way for endogenous stem cells to generate appropriate replacements is a main goal of regenerative medicine. Using single-cell transcriptome and chromatin accessibility analysis, Enric Llorens-Bobadilla and colleagues discovered that mouse ependymal cells possess the latent ability to differentiate into oligodendrocytes and help repair spinal cord damage in mice. Llorens-Bobadilla et al. demonstrate that the oligodendrogenic program, which is normally latent in adult ependymal cells, can be activated by expressing the transcription factor Olig2. Induced in vivo expression of Olig2 after spinal cord injury triggered local ependymal cells to rapidly produce new oligodendrocytes, which aided in axon repair and improved neural communication near the site of the damage.