Injuring neurons induces neuronal differentiation in a population of hippocampal precursor cells in culture.

A novel population of hippocampal precursor cells (HPCs) that can be induced to differentiate into astrocytes and oligodendrocytes can be derived from hippocampal cultures grown in serum-free media. The HPCs are PDGF-responsive, do not proliferate with bFGF, and grow as sheets of cells rather than gathering into neurospheres. The HPCs share many markers (A2B5, GD3, poly-sialylated neuronal common adhesion molecule (PSA-NCAM), and NG2) with oligodendrocyte precursor cells (OPCs). The HPCs do not express markers for mature neurons, astrocytes, or oligodendrocytes. Like OPCs, the HPCs differentiate into glial fibrillary acidic protein (GFAP)+ astrocytes and GalC+ oligodendrocytes with the addition of bone morphogenetic protein-4 (BMP-4) and triiodothyronine (T3), respectively. They do not differentiate into neurons with the addition or withdrawal of basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), or retinoic acid (RA). These HPCs can be stimulated to differentiate into neuron-like cells by the induction of neuronal injury or cell death in nearby cultured neurons or by conditioned medium from injured neuronal cultures. Under these conditions, HPCs grow larger, develop more extensive dendritic processes, become microtubule-associated protein-2-immunoreactive, express large voltage-dependent sodium currents, and form synaptic connections. The conversion of endogenous pluripotent precursor cells into neurons in response to local brain injury may be an important component of central nervous system homeostasis.