Adult neural stem cell pools in homeostasis and pathogenesis.

Abstract

Adult neural stem cells (NSCs) persist throughout life in discrete neurogenic niches of the mammalian brain, most prominently the subventricular zone (SVZ), the subgranular zone (SGZ) of the hippocampal dentate gyrus, and the hypothalamic ventricular zone (HVZ). These niches harbor regionally specialized NSC populations that support neural plasticity, cognitive and emotional regulation, and, in the hypothalamus, systemic metabolic and neuroendocrine homeostasis. While adult neurogenesis in the SGZ and SVZ has been extensively characterized, the HVZ has emerged as a functional adult NSC niche linking stem cell regulation to whole-body physiology. Here, we review recent advances across the SGZ, SVZ, and HVZ to define shared organizational principles and region-specific regulatory mechanisms governing adult NSC identity, homeostasis, and lineage output. We also highlight how intrinsic transcriptional programs, metabolic states, and niche-derived signals shape NSC behavior in each region, and how aging, inflammation, and metabolic stress differentially disrupt these processes. By integrating insights from both classical and hypothalamic neurogenic niches, this review provides a unified framework for understanding adult NSC diversity and disease susceptibility, and discusses strategies to modulate endogenous stem cell niches to preserve homeostasis and minimize disease risk.