Identification of a discrete subpopulation of spinal cord ependymal cells with neural stem cell properties
Moa Stenudd, Hanna Sabelström, Enric Llorens-Bobadilla, Margherita Zamboni, Hans Blom, Hjalmar Brismar, Shupei Zhang, Onur Başak, Hans Clevers, Christian Göritz, Fanie Barnabé‐Heider, Jonas Frisén
Abstract
Spinal cord ependymal cells display neural stem cell properties in vitro and generate scar-forming astrocytes and remyelinating oligodendrocytes after injury. We report that ependymal cells are functionally heterogeneous and identify a small subpopulation (8% of ependymal cells and 0.1% of all cells in a spinal cord segment), which we denote ependymal A (EpA) cells, that accounts for the in vitro stem cell potential in the adult spinal cord. After spinal cord injury, EpA cells undergo self-renewing cell division as they give rise to differentiated progeny. Single-cell transcriptome analysis revealed a loss of ependymal cell gene expression programs as EpA cells gained signaling entropy and dedifferentiated to a stem-cell-like transcriptional state after an injury. We conclude that EpA cells are highly differentiated cells that can revert to a stem cell state and constitute a therapeutic target for spinal cord repair.