Prosurvival factors derived from the embryonic brain promote adult neural stem cell survival.

Abstract

Temporally distinct populations of neural stem cells (NSCs; embryonic and adult) display the cardinal stem cell properties of self-renewal and multipotentiality; however, their relative frequency and cell kinetics vary through development and into old age. We asked whether changes in NSC behavior could be accounted for by changes in environmental signals over time. We identified a prosurvival signaling cascade that enhances adult-derived NSC survival using cues released from embryonic neurons. Specifically, we demonstrate that stromal-cell-derived factor-1α (SDF-1α) released by embryonic neurons leads to upregulation of neuronal nitric oxide synthase in adult neural precursor cells. The resulting increase in nitric oxide leads to the upregulation of the stem cell factor (SCF) receptor ckit on adult NSCs (ANSCs). SCF released from embryonic neurons results in enhanced NSC survival. Using both in vitro and in vivo assays, we have demonstrated expansion of the size of the NSC pool through this pathway, indicating that ANSCs retain their ability to respond to embryonic-derived cues into adulthood.