Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics

View ORCID ProfileMeng Zhang, Stephen W. Eichhorn, Brian Zingg, View ORCID ProfileZizhen Yao, View ORCID ProfileHongkui Zeng, View ORCID ProfileHongwei Dong, View ORCID ProfileXiaowei Zhuang
doi: https://doi.org/10.1101/2020.06.04.105700
Meng Zhang
1Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
3Department of Physics, Harvard University, Cambridge, MA 02138, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Meng Zhang
Stephen W. Eichhorn
1Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
3Department of Physics, Harvard University, Cambridge, MA 02138, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian Zingg
4Center for Integrative Connectomics, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90095, USA
5Department of Neurology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90095, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zizhen Yao
6Allen Institute for Brain Science, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zizhen Yao
Hongkui Zeng
6Allen Institute for Brain Science, Seattle, WA 98109, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hongkui Zeng
Hongwei Dong
4Center for Integrative Connectomics, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90095, USA
5Department of Neurology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, 90095, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hongwei Dong
Xiaowei Zhuang
1Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
2Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
3Department of Physics, Harvard University, Cambridge, MA 02138, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Xiaowei Zhuang
  • For correspondence: zhuang@chemistry.harvard.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

A mammalian brain is comprised of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing provides a powerful approach to identify cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain1-3. Single-cell epigenomic profiling4,5 further provides information on gene-regulatory signatures of different cell types. Understanding how different cell types contribute to brain function, however, requires knowledge of their spatial organization and connectivity, which is not preserved in sequencing-based methods that involve cell dissociation3,6. Here, we used an in situ single-cell transcriptome-imaging method, multiplexed error-robust fluorescence in situ hybridization (MERFISH)7, to generate a molecularly defined and spatially resolved cell atlas of the mouse primary motor cortex (MOp). We profiled ∼300,000 cells in the MOp, identified 95 neuronal and non-neuronal cell clusters, and revealed a complex spatial map in which not only excitatory neuronal clusters but also most inhibitory neuronal clusters adopted layered organizations. Notably, intratelencephalic (IT) cells, the largest branch of neurons in the MOp, formed a continuous spectrum of cells with gradual changes in both gene expression profiles and cortical depth positions in a highly correlated manner. Furthermore, we integrated MERFISH with retrograde tracing to probe the projection targets for different MOp neuronal cell types and found that projections of MOp neurons to other cortical regions formed a many-to-many network with each target region receiving input preferentially from a different composition of IT clusters. Overall, our results provide a high-resolution spatial and projection map of molecularly defined cell types in the MOp. We anticipate that the imaging platform described here can be broadly applied to create high-resolution cell atlases of a wide range of systems.

Competing Interest Statement

X. Z. is a co-founder of Vizgen.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 05, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics
Meng Zhang, Stephen W. Eichhorn, Brian Zingg, Zizhen Yao, Hongkui Zeng, Hongwei Dong, Xiaowei Zhuang
bioRxiv 2020.06.04.105700; doi: https://doi.org/10.1101/2020.06.04.105700
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Molecular, spatial and projection diversity of neurons in primary motor cortex revealed by in situ single-cell transcriptomics
Meng Zhang, Stephen W. Eichhorn, Brian Zingg, Zizhen Yao, Hongkui Zeng, Hongwei Dong, Xiaowei Zhuang
bioRxiv 2020.06.04.105700; doi: https://doi.org/10.1101/2020.06.04.105700

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4087)
  • Biochemistry (8762)
  • Bioengineering (6479)
  • Bioinformatics (23341)
  • Biophysics (11750)
  • Cancer Biology (9149)
  • Cell Biology (13248)
  • Clinical Trials (138)
  • Developmental Biology (7417)
  • Ecology (11369)
  • Epidemiology (2066)
  • Evolutionary Biology (15087)
  • Genetics (10399)
  • Genomics (14009)
  • Immunology (9121)
  • Microbiology (22040)
  • Molecular Biology (8779)
  • Neuroscience (47368)
  • Paleontology (350)
  • Pathology (1420)
  • Pharmacology and Toxicology (2482)
  • Physiology (3704)
  • Plant Biology (8050)
  • Scientific Communication and Education (1431)
  • Synthetic Biology (2208)
  • Systems Biology (6016)
  • Zoology (1249)