Lineage tracing reveals the origin of Nestin-positive cells are heterogeneous and rarely from ependymal cells after spinal cord injury.

Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury (SCI), Nestin expression is reactivated and Nestin-positive (Nestin+) cells aggregate at the injury site. However, the derivation of Nestin+ cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin+ cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP+ astrocytes were the main cell type that expressed Nestin; they then formed an astrocyte scar. In the lesion core, Nestin+ cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin+ cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair.