Single-nucleus RNA-seq characterizes the cell types along the neuronal lineage in the adult human subependymal zone and reveals reduced oligodendrocyte progenitor abundance with age.

The subependymal zone (SEZ), also known as the subventricular zone (SVZ), constitutes a neurogenic niche that persists during post-natal life. In humans, the neurogenic potential of the SEZ declines after the first year of life. However, studies discovering markers of stem and progenitor cells highlight the neurogenic capacity of progenitors in the adult human SEZ, with increased neurogenic activity occurring under pathological conditions. In the present study, the complete cellular niche of the adult human SEZ was characterized by single-nucleus RNA sequencing, and compared between 4 youth (age 16-22) and 4 middle-aged adults (age 44-53). We identified 11 cellular clusters including clusters expressing marker genes for neural stem cells (NSCs), neuroblasts, immature neurons and oligodendrocyte progenitor cells. The relative abundance of NSC and neuroblast clusters did not differ between the two age groups, indicating that the pool of SEZ NSCs does not decline in this age range. The relative abundance of oligodendrocyte progenitors and microglia decreased in middle-age, indicating that the cellular composition of human SEZ is remodeled between youth and adulthood. The expression of genes related to nervous system development was higher across different cell types, including NSCs, in youth as compared to middle-age. These transcriptional changes suggest ongoing central nervous system plasticity in the SEZ in youth, which is declined by middle-age. Significance statement In the present study, single-nuclei analysis and immunostainings were performed to characterize the complete cellular niche of the adult human subependymal zone (SEZ), including youth and middle-aged donors. The authors identified most cell types found along the neuronal lineage, from neural stem cells (NSCs), neuroblasts, immature and mature neurons, providing evidence of ongoing neurogenesis in the human SEZ neurogenic niche of youth and adults.