DNGR-1-tracing marks an ependymal cell subset with damage-responsive neural stem cell potential

• Published in: Developmental cell 2022-08, Vol.57 (16), p.1957-1975.e9
• Main Authors: Frederico, Bruno, Martins, Isaura, Chapela, Diana, Gasparrini, Francesca, Chakravarty, Probir, Ackels, Tobias, Piot, Cécile, Almeida, Bruna, Carvalho, Joana, Ciccarelli, Alessandro, Peddie, Christopher J., Rogers, Neil, Briscoe, James, Guillemot, François, Schaefer, Andreas T., Saúde, Leonor, Reis e Sousa, Caetano
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; CLEC9A; dendritic cells; Ependyma; ependymal cells; Mammals; Mice; Neural Stem Cells; Neuroglia; Spinal Cord; tissue repair
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2022.07.012

Cells with latent stem ability can contribute to mammalian tissue regeneration after damage. Whether the central nervous system (CNS) harbors such cells remains controversial. Here, we report that DNGR-1 lineage tracing in mice identifies an ependymal cell subset, wherein resides latent regenerative potential. We demonstrate that DNGR-1-lineage-traced ependymal cells arise early in embryogenesis (E11.5) and subsequently spread across the lining of cerebrospinal fluid (CSF)-filled compartments to form a contiguous sheet from the brain to the end of the spinal cord. In the steady state, these DNGR-1-traced cells are quiescent, committed to their ependymal cell fate, and do not contribute to neuronal or glial lineages. However, trans-differentiation can be induced in adult mice by CNS injury or in vitro by culture with suitable factors. Our findings highlight previously unappreciated ependymal cell heterogeneity and identify across the entire CNS an ependymal cell subset wherein resides damage-responsive neural stem cell potential. [Display omitted] •DNGR-1 is expressed early in mouse embryogenesis in a subset of ventricular progenitors•DNGR-1 tracing shows that those progenitors give rise to a subset of ependymal cells•DNGR-1-traced ependymal cells have latent regenerative potential•DNGR-1-traced ependymal cells can be mobilized by local injury Frederico et al. show that embryonic DNGR-1 expression marks a population of ventricular progenitors committed to an ependymal cell subset yet endowed with damage-responsive neural stem cell potential in adulthood. Trans-differentiation can by induced in vitro with appropriate factors or in vivo after CNS injury.