The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic
capabilities in many species, and is selectively vulnerable to Alzheimer's disease.
To investigate neurogenic potential and cellular diversity, we profiled single-nucleus
transcriptomes in five hippocampal-entorhinal subregions in humans, macaques, and
pigs. Integrated cross-species analysis revealed robust transcriptomic and histologic
signatures of neurogenesis in the adult mouse, pig, and macaque but not humans. Doublecortin
(DCX), a widely accepted marker of newly generated granule cells, was detected in
diverse human neurons, but it did not define immature neuron populations. To explore
species differences in cellular diversity and implications for disease, we characterized
subregion-specific, transcriptomically defined cell types and transitional changes
from the three-layered archicortex to the six-layered neocortex. Notably, METTL7B
defined subregion-specific excitatory neurons and astrocytes in primates, associated
with endoplasmic reticulum and lipid droplet proteins, including Alzheimer's disease-related
proteins. This resource reveals cell-type- and species-specific properties shaping
hippocampal-entorhinal neurogenesis and function.