A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain

TLDR

The diversity of cell types and regulatory states in the brain, and how these change during aging, remains largely unknown. The study presents a single‑cell transcriptome atlas of the entire adult Drosophila melanogaster brain sampled across its lifespan. The atlas was built by clustering 87 initial cell clusters, further subclustered and validated by targeted cell‑sorting, covering nearly all brain cells and integrated into the SCope platform (http://scope.aertslab.org). The atlas reveals high granularity with a wide range of cell types, regulatory heterogeneity linked to energy consumption, and an exponential decline in RNA content during aging without loss of neuronal identity, enabling comprehensive exploration of transcriptional states.

Abstract

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.