Spatial transcriptomics analysis of adult hippocampal neurogenesis in the human brain
Adult hippocampal neurogenesis (AHN) has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in post-mortem human hippocampal samples by combining spatial transcriptomics and fluorescent in situ hybridization. We detected very few cells expressing neural stem cell- and proliferation-specific genes in the human dentate gyrus (DG) from childhood to middle age, suggesting very low levels of hippocampal neurogenesis throughout life. However, we observed at all ages a significant number of DG cells expressing the immature neuronal marker DCX. The majority of DCX+ cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature. Overall, our study investigates for the first time the extent of AHN in the human brain with spatial transcriptomic tools and reveals important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus. Overall design: Four fresh-frozen dentate gyrus samples from neurologically healthy male control subjects (21, 26, 42 and 43 years old) were used for spatial transcriptomics and analyzed.