WHOLE BRAIN SINGLE NUCLEUS TRANSCRIPTOMICS IN HUMAN: WHAT WE KNOW SO FAR

Although single-cell RNA sequencing has revolutionized our understanding of the mammalian brain, the diversity of cell types that contribute to the human brain remains poorly understood. We therefore used high-throughput single-nucleus RNA sequencing to survey the entire adult human brain. We sampled tissue from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Fluorescence-activated nuclei sorting enriched for neurons. The final dataset contained over three million nuclei, among which our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins. Non-cortical regions like the hypothalamus, midbrain, and hindbrain comprised a remarkably high diversity of neurons. Glial cells also exhibited regional diversity at multiple scales: astrocytes and oligodendrocyte precursors clustered into subtypes specific to the telencephalon -- the developmental compartment that gives rise to the cortex, hippocampus, and cerebral nuclei -- and non-telencephalic regions of the brain; astrocytes exhibited finer-scale regional diversity. Our findings therefore suggest a unique cellular composition of the telencephalon with respect to all major brain cell types. As the first single-cell transcriptomic census of the entire human brain, these data provide a novel resource for understanding the molecular diversity of the human brain in health and disease. None