The hippocampal subgranular zone neurogenic niche: a modular perspective on neural stem cell regulation.

The subgranular zone (SGZ) of the hippocampus represents a principal site of adult neurogenesis and exhibits distinct structural and organizational features. Increasing evidence indicates that neural stem cell (NSC) behavior in the SGZ is not solely determined by intrinsic cellular properties, but is critically shaped by its surrounding neurogenic niche. However, current studies largely describe niche-derived regulatory factors in isolation, and a systematic framework integrating these diverse signals remains lacking. In this review, we propose a structured perspective that links the unique anatomical and organizational characteristics of the SGZ to its regulatory mechanisms. We conceptualize SGZ niche regulation as a multi-dimensional and non-hierarchical system, in which multiple interacting components-including spatial organization, metabolic-vascular support, neural circuit activity, immune modulation, and extracellular matrix-mediated signaling-collectively govern NSC state transitions. Within this framework, neurogenesis is understood as an emergent outcome of coordinated changes across these regulatory dimensions rather than the result of single-factor control. We further discuss how shifts in the neurogenic niche under pathological conditions-such as aging, Alzheimer's disease, and chronic cerebral hypoperfusion (CCH) -reshape NSC behavior, driving maladaptive responses that may ultimately lead to dysregulated neurogenesis. By providing a modular and system-level perspective, this review offers a conceptual basis for understanding SGZ regulation and may help identify potential targets for restoring neurogenic capacity.