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 Nestinpositive(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.