Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans

Abstract Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans remains extensive debates1-8. Here, to provide a better understanding of AHN of primates, droplet-based single nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. We pinpoint the dynamics of the neurogenic lineage, including adult neural stem cells (NSCs) and immature neurons, and the diversity of astrocytes and microglia. In the neurogenic lineage, the regulatory continuum from adult NSCs to immature and mature granule cells is investigated. We identify ETNPPL as a primate-specific NSC marker and verify STMN1 and STMN2 as immature neuron markers in primates. Importantly, we also illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis implies that astrocytes are more important niche cells that provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and thus are attributed to the decrease and variability of AHN in adult and elderly.