Cited by 840Single-cell and spatial transcriptomicsGenetics, Aging, and Longevity in Model OrganismsNeurobiology and Insect Physiology Research

A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain

Open access
Davie, Kristofer, Janssens, Jasper, Koldere, Duygu, De Waegeneer, Maxime, Pech, Uli, Kreft, Łukasz, Aibar, Sara, Makhzami, Samira +16 more·2018·Cell

Published version of a preprint

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.

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Registry

Crossref · 10.1016/j.cell.2018.05.057

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  • While transmitter-related gene expression and immunoreactivity are largely exclusive between the fast-acting transmitters in flies, most neuropeptides and monoamines can co-transmit with fast-acting transmitters.

    “While transmitter-related gene expression and immunoreactivity are largely exclusive between the fast-acting transmitters in flies,21,22,30,31 most neuropeptides and monoamines can co-transmit with fast-acting transmitters.21,163”

    From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [22]

    The Results sections on adult-brain cell types and regulatory networks identify distinct cholinergic, glutamatergic, and GABAergic groups, and the rare-cell-types section says neuropeptides are expressed in some other cell types. These passages support parts of the gene-expression account, but they do not establish immunoreactivity, show that most neuropeptides or monoamines co-transmit with fast-acting transmitters, or measure co-transmission itself. No page numbers are available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured
  • Our results are conceptually consistent with previous reports of large transcriptional changes with age in some cell identities and more subtle changes in others.

    “Our results are conceptually consistent with previous reports of large transcriptional changes with age in some cell identities and more subtle changes in others (Kowalczyk et al. 2015; Keyes et al. 2016; Davie et al. 2018; Keyes and Fuchs 2018).”
  • Transcriptomic atlases of the central adult brain and optic lobes are appearing.

    “Transcriptomic atlases of the central adult brain95,132 and optic lobes133,134 are appearing.”

    From Neuronal wiring diagram of an adult brain (2023) · cites this paper as [132]

  • Aging dramatically reduces amount of RNA in Drosophila brain cells.

    “Aging dramatically reduces the amount of RNA in Drosophila brain cells (Davie et al., 2018).”

    From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Davie et al., 2018

  • Metabolic processes, like oxygen consumption and mitochondrial function, are broadly modulated to keep pace with both development and plasticity, consistent with prior reports in neurodevelopment.

    “Also, metabolic processes, like oxygen consumption and mitochondrial function are broadly modulated to keep pace with both development and plasticity, consistent with prior reports in neurodevelopment28 (Fig. 4e).”

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Authors
Davie, K., Janssens, J., Koldere, D., De Waegeneer, M., Pech, U., Kreft, Ł., Aibar, S., Makhzami, S., Christiaens, V., Bravo González-Blas, C., Poovathingal, S., Hulselmans, G., Spanier, K. I., Moerman, T., Vanspauwen, B., Geurs, S., Voet, T., Lammertyn, J., Thienpont, B., Liu, S., Konstantinides, N., Fiers, M., Verstreken, P., & Aerts, S.
Affiliations
  • VIB-KU Leuven Center for Brain & Disease Research (BE)
  • Vlaams Instituut voor Biotechnologie (BE)
  • IMEC (BE)
  • KU Leuven (BE)
Corresponding author
Aerts, Stein
Venue
Cell
Publisher
Elsevier BV
Published
2018-08
Volume
174
Issue
4
Pages
982-998.e20
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2807884764
Cited by
840
References
109
Citations by year
2026: 70 · 2025: 136 · 2024: 112 · 2023: 116 · 2022: 99 · 2021: 113 · 2020: 108 · 2019: 65 · 2018: 21
FWCI
27.93
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
Funders
  • The Research Foundation - Flanders (G.0640.13, G.0791.14)
  • Special Research Fund (BOF) KU Leuven (PF/10/016, OT/13/103, Opening the Future” grant, Methusalem Grant (3M140280))
  • Flemish Government (ERC consolidator, 646671 RobustSynapses, 724226 cis-CONTROL, PDM/16/188)
  • agency for Innovation by Science and Technology (141509, 1199518N)
  • Deutsche Forschungsgemeinschaft (808066)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
brain aging, Drosophila melanogaster, single-cell transcriptome atlas, neuronal cell types, cellular heterogeneity, gene regulatory networks, energy metabolism
MeSH terms
Aging, Animals, Brain, Drosophila melanogaster, Female, Male, Gene Expression Profiling, Drosophila Proteins, Gene Regulatory Networks, Single-Cell Analysis, Transcriptome

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