The cellular diversity in the human brain is underpinned by neural progenitor cells(NPCs). The dentate gyrus (DG) of the mammalian hippocampus maintains a NPC population into adulthood. However, the organization of NPCs in the human hippocampus remain poorly characterized. Here, we provide a map of the developmental trajectory of NPCs in the human DG, combining multimodal transcriptomic analysis within a neuroanatomical context. We observed cellular changes in the hippocampus at mid-gestation, coinciding with the emergence of a NPClayer within the DG, termed the granular-hilar progenitor zone (GHPZ). Neurogenic signatures in the GHPZ diminished by infancy, coinciding with reduced NPC numbers as they progressed toward an astrocytic program. Lastly, we validated WNT-associated genes as NPC markers in the developing human DG. Our study defines the decline of NPCs from gestation to the postnatal period and sets the molecular blueprintfor NPC identification in the human DG.
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