- The potential of a neural stem cell line to acquire cholinergic characteristics was studied in transplants injected into the septum/diagonal band nuclei of young adult rats and mice. The stem cells integrated within the nuclei and survived for up to 9 months. Three methods were used to identify the grafted cells and to show differentiation into astrocytes and neurons. Enhanced survival of the stem cells occurred in the host brain with a previous lesion of the fimbria-fornix pathway. Differentiated cells acquired neuronal-like features including the expression of neurofilament subunits. In lesioned hosts, subpopulations of the grafted cells acquired a cholinergic neuronal phenotype and expressed choline acetyltransferase and the p75 neurotrophin receptor. Cells that developed into astrocytes were often associated with blood vessels and expressed glial fibrillary acidic protein. The results further exemplify the potential of stem cell lines and the property of site-specific differentiation when this line is transplanted to the cholinergic system of the adult brain.