A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain

The diversity of cell types and regulatory states in the brain, and how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas of the entire adult Drosophila melanogaster brain sampled across its lifespan. Cell clustering identified 87 initial cell clusters that are further subclustered and validated by targeted cell-sorting. Our data show high granularity and identify a wide range of cell types. Gene network analyses using SCENIC revealed regulatory heterogeneity linked to energy consumption. During aging, RNA content declines exponentially without affecting neuronal identity in old brains. This single-cell brain atlas covers nearly all cells in the normal brain and provides the tools to study cellular diversity alongside other Drosophila and mammalian single-cell datasets in our unique single-cell analysis platform: SCope (http://scope.aertslab.org). These results, together with SCope, allow comprehensive exploration of all transcriptional states of an entire aging brain. [Display omitted] •A single-cell atlas of the adult fly brain during aging•Network inference reveals regulatory states related to oxidative phosphorylation•Cell identity is retained during aging despite exponential decline of gene expression•SCope: An online tool to explore and compare single-cell datasets across species A single-cell atlas of adult fly brains identifies the ensemble of neuronal and glial cell types and their dynamic changes during aging.