Project description:The diversity of cell types and regulatory states in the brain, and how these change during ageing, 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 shows high granularity and identifies a wide range of cell types. Gene network analyses using SCENIC revealed regulatory heterogeneity linked to energy consumption. During ageing, 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. These results allow comprehensive exploration of all transcriptional states of an entire ageing brain.
Project description:The cellular composition of the brain and how it is affected by starvation, remains largely unknown. Here we introduce a single-cell transcriptome atlas of the entire Drosophila melanogaster first instar larval brain. We first assigned cell type identity based on the expression of previously characterized marker genes, allowing us to distinguish five major groups: neural progenitors cells, differentiated neurons, glial cells, undifferentiated neurons as well as non-neural cells corresponding to organs and structures located adjacent to the brain. All major classes were further subdivided into multiple subtypes based on cluster analysis, revealing critical biological features of various cell types. Moreover, we included two different feeding conditions: normal fed versus starved. After starvation, the transcriptional profile of several cell clusters were altered, while the overall composition of the brain remains unaffected. Intriguingly, different cell clusters show very distinct responses to starvation, suggesting the presence of cell-specific programs for nutrition availability. Establishing a single-cell transcriptome atlas of the larval brain provides a powerful tool to explore cell diversity, assess genetic profiles of neurogenic, neuronal and glial cell types. The analysis of neurotransmitters, neuropeptides and their respective receptors may further open the doors for functional studies.
Project description:We have shown previously that older flies are intrinsically more susceptible to Aβ42 toxicity. Building upon these findings, this study aimed to determine the mechanisms by which ageing increases this vulnerability to damage in the brain. A fixed dose of Aβ42 peptide was induced in young (5d) versus older (20d) fly neurons, and then gene and protein expression changes examined in dissected fly brains using microarray analyses. This unbiased approach has revealed genes and pathways that correlate with increased susceptibility of the ageing brain to proteotoxicity.
Project description:Single-cell mRNA sequencing (mRNA-seq) technologies are reshaping the current cell-type classification system. In previous studies, we built the mouse cell atlas (MCA) and human cell landscape (HCL) to catalog all cell types by collecting scRNA-seq data. However, systematically study for zebrafish (Danio rerio) and fruit fly (Drosophila melanogaster) are still lacking. Here, we construct the zebrafish and Drosophila cell atlas with Microwell-seq protocols, which provides valuable resources for characterization of diverse cell populations of zebrafish and Drosophila, and studying difference between vertebrates and Invertebrates at single cell level.