Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons

Abstract

Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage—neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

Data availability

Raw sequencing reads and preprocessed sequence data have been deposited in GEO under accession code GSE161228.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Qijing Xie

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Brbic

    Department of Computer Science, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Felix Horns

    Biophysics Graduate Program, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5872-5061
  4. Sai Saroja Kolluru

    Department of Bioengineering, Chan Zuckerberg Biohub, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert C Jones

    Department of Bioengineering, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7235-9854
  6. Jiefu Li

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0062-4652
  7. Anay R Reddy

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Anthony Xie

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sayeh Kohani

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhuoran Li

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Colleen N McLaughlin

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Tongchao Li

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Chuanyun Xu

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. David Vacek

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. David J Luginbuhl

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Jure Leskovec

    Department of Computer Science, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Stephen R Quake

    Chan Zuckerberg Biohub, San Francisco, United States
    For correspondence
    steve@quake-lab.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1613-0809
  18. Liqun Luo

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    For correspondence
    lluo@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5467-9264
  19. Hongjie Li

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01 DC005982)

  • Liqun Luo

National Institutes of Health (1K99AG062746)

  • Hongjie Li

Howard Hughes Medical Institute

  • Liqun Luo

Stanford University (Graduate Student Fellowship)

  • Qijing Xie

Wu Tsai Neuroscience Institute at Stanford (Interdisciplinary postdoctoral scholar)

  • Hongjie Li

We Tsai Neuroscience Institute at Stanford (Neuro-omics program)

  • Liqun Luo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Version history

  1. Received: September 25, 2020
  2. Accepted: January 5, 2021
  3. Accepted Manuscript published: January 11, 2021 (version 1)
  4. Version of Record published: February 8, 2021 (version 2)

Copyright

© 2021, Xie et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,214
    Page views
  • 568
    Downloads
  • 22
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Qijing Xie
  2. Maria Brbic
  3. Felix Horns
  4. Sai Saroja Kolluru
  5. Robert C Jones
  6. Jiefu Li
  7. Anay R Reddy
  8. Anthony Xie
  9. Sayeh Kohani
  10. Zhuoran Li
  11. Colleen N McLaughlin
  12. Tongchao Li
  13. Chuanyun Xu
  14. David Vacek
  15. David J Luginbuhl
  16. Jure Leskovec
  17. Stephen R Quake
  18. Liqun Luo
  19. Hongjie Li
(2021)
Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons
eLife 10:e63450.
https://doi.org/10.7554/eLife.63450

Share this article

https://doi.org/10.7554/eLife.63450

Further reading

    1. Neuroscience
    Lies Deceuninck, Fabian Kloosterman
    Research Article Updated

    Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay – a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.

    1. Neuroscience
    Sydney Trask, Nicole C Ferrara
    Insight

    Gradually reducing a source of fear during extinction treatments may weaken negative memories in the long term.