Molecular landscape of immature neurons in the human hippocampus across the lifespan

Immature neurons arising from adult neurogenesis contribute to plasticity and unique functionsinthe adult mammalian brain. Whether immature dentate granule cells (imGCs) exist in the adult human hippocampusis under debate. Herewe performedsingle-nucleus transcriptomicanalysis aided by a validated machinelearning approach to quantify the abundance of imGCs in the 5postnatal human hippocampus and to investigate their molecular properties. We show the sustained presence of human imGCs through prenatal, infant, child, adolescent, adult,andaging stages andreveal their shared and differentmolecular characteristicsacross agesandspecies. Furthermore, we directly demonstrate the capacity for neurogenesis in the postnatal human hippocampus using surgical specimensin culture. Together, these resultsprovide novel insights10into molecular propertiesof imGCs in humans across the lifespan. Overall design: single nucleus RNA-seq on human hippocampus