A single-cell catalogue of regulatory states in the ageing Drosophila brain

Abstract

SummaryThe diversity of cell types and regulatory states in the brain, and how these change during ageing, remains largely unknown. Here, we present a single-cell transcriptome catalogue of the entire adult Drosophila melanogaster brain sampled across its lifespan. Both neurons and glia age through a process of "regulatory erosion", characterized by a strong decline of RNA content, and accompanied by increasing transcriptional and chromatin noise. We identify more than 50 cell types by specific transcription factors and their downstream gene regulatory networks. In addition to neurotransmitter types and neuroblast lineages, we find a novel neuronal cell state driven by datilografo and prospero. This state relates to neuronal birth order, the metabolic profile, and the activity of a neuron. Our single-cell brain catalogue reveals extensive regulatory heterogeneity linked to ageing and brain function and will serve as a reference for future studies of genetic variation and disease mutations.not peer-reviewed)

Substrates for Neuronal Cotransmission With Neuropeptides and Small Molecule Neurotransmitters in Drosophila

“…Furthermore, reports published so far on mapping of coexpression to specific neurons are likely to cover only a small fraction of the actual cases. This is suggestive from a few recent reports analyzing transcriptomes of single dissociated cells in the Drosophila brain where preliminary data already uncovered plenty of new combinations of colocalized substances ( Abruzzi et al, 2017 ; Croset et al, 2017 ; Davie et al, 2017 ) shown in Tables 3 , 4 . These novel data constitute a rich source for future systematic mapping of neuropeptides and SMNs to neurons and circuits in the brain of Drosophila by imaging techniques.…”

“…The studies discussed above are based on traditional imaging techniques and have probably only revealed the tip of the iceberg. Recently, reports on single-cell transcriptomics of dissociated Drosophila brain neurons discovered numerous additional patterns of colocalized neuropeptides and neuropeptides with SMNs ( Abruzzi et al, 2017 ; Croset et al, 2017 ; Davie et al, 2017 ), shown in Tables 3 , 4 . Although this type of analysis substantially increased the cases of likely colocalization of neuropeptides and monoamines, as well as other SMNs, it provides little information on which specific types of neurons that express the substances.…”

“…The repertoire of possible actions of colocalized substances in insects has been extended substantially with the discovery that also neurosecretory cells and gut endocrine cells can produce multiple peptide hormones that may act both locally in paracrine signaling, at peripheral targets and in certain neuronal circuits in the CNS to orchestrate physiology and behavior ( Veenstra et al, 2008 ; Kahsai et al, 2010 ; Nässel and Winther, 2010 ; Veenstra and Ida, 2014 ; Wegener and Veenstra, 2015 ; Zandawala et al, 2018 ). More recently, studies employing single cell transcriptomics have expanded the list of colocalized neuroactive substances in Drosophila neurons ( Abruzzi et al, 2017 ; Croset et al, 2017 ; Davie et al, 2017 ).…”

Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

“…Our initial analysis was performed on 10,286 of the highest quality cells (≥800 UMIs) from a larger dataset of 19,260 cells. This atlas is effectively a scaffold that can now be continuously updated and expanded as additional cells are collected and sequenced ( Davie et al, 2017 ; Konstantinides et al, 2018 ). Our current dataset was derived from cells taken from unique groups of flies, processed on eight separate days, and yet each biological replicate contributed equally to the combined data set.…”

FMRFa receptor stimulated Ca2+signals alter the activity of flight modulating central dopaminergic neurons inDrosophila melanogaster

“…Furthermore, co-expression of the dopamine synthesizing enzyme Tyrosine Hydroxylase (TH) in a few neurons marked by an FMRFaGAL4 (48), suggests the existence of an autocrine signaling mechanism within the flight modulating dopaminergic neurons. This idea is supported by recent studies of single cell sequencing of Drosophila neurons where FMRFa transcripts were seen in a small number of central brain dopaminergic neurons (49, 50). Interestingly, a recent report from Manduca demonstrated that an FMRFa positive neuron lies at the center of a putative sensory-motor circuit for integration of olfactory stimuli with wing movements during flight (51).…”