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

Highly multiplexed spatially resolved gene expression profiling of mouse organogenesis

View ORCID ProfileT. Lohoff, View ORCID ProfileS. Ghazanfar, View ORCID ProfileA. Missarova, View ORCID ProfileN. Koulena, N. Pierson, View ORCID ProfileJ.A. Griffiths, View ORCID ProfileE.S. Bardot, C.-H.L. Eng, R.C.V. Tyser, View ORCID ProfileR. Argelaguet, View ORCID ProfileC. Guibentif, View ORCID ProfileS. Srinivas, View ORCID ProfileJ. Briscoe, View ORCID ProfileB.D. Simons, A.-K. Hadjantonakis, B. Göttgens, W. Reik, J. Nichols, L. Cai, J.C. Marioni
doi: https://doi.org/10.1101/2020.11.20.391896
T. Lohoff
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
2Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
3Epigenetics Programme, Babraham Institute, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for T. Lohoff
S. Ghazanfar
4Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for S. Ghazanfar
A. Missarova
4Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for A. Missarova
N. Koulena
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for N. Koulena
N. Pierson
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J.A. Griffiths
4Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for J.A. Griffiths
E.S. Bardot
7Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for E.S. Bardot
C.-H.L. Eng
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R.C.V. Tyser
8Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Argelaguet
5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for R. Argelaguet
C. Guibentif
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
9Department of Haematology, University of Cambridge, Cambridge, UK
10Sahlgrenska Cancer Center, Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for C. Guibentif
S. Srinivas
8Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for S. Srinivas
J. Briscoe
11The Francis Crick Institute, London NW1 1AT, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for J. Briscoe
B.D. Simons
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
12The Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK
13Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for B.D. Simons
A.-K. Hadjantonakis
7Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. Göttgens
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
9Department of Haematology, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. Reik
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
3Epigenetics Programme, Babraham Institute, Cambridge, UK
14Centre for Trophoblast Research, University of Cambridge, Cambridge, UK
15Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wolf.reik@babraham.ac.uk jn270@cam.ac.uk lcai@caltech.edu marioni@ebi.ac.uk
J. Nichols
1Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
2Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wolf.reik@babraham.ac.uk jn270@cam.ac.uk lcai@caltech.edu marioni@ebi.ac.uk
L. Cai
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wolf.reik@babraham.ac.uk jn270@cam.ac.uk lcai@caltech.edu marioni@ebi.ac.uk
J.C. Marioni
4Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
15Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wolf.reik@babraham.ac.uk jn270@cam.ac.uk lcai@caltech.edu marioni@ebi.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Transcriptional and epigenetic profiling of single-cells has advanced our knowledge of the molecular bases of gastrulation and early organogenesis. However, current approaches rely on dissociating cells from tissues, thereby losing the crucial spatial context that is necessary for understanding cell and tissue interactions during development. Here, we apply an image-based single-cell transcriptomics method, seqFISH, to simultaneously and precisely detect mRNA molecules for 387 selected target genes in 8-12 somite stage mouse embryo tissue sections. By integrating spatial context and highly multiplexed transcriptional measurements with two single-cell transcriptome atlases we accurately characterize cell types across the embryo and demonstrate how spatially-resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain-hindbrain boundary and the developing gut tube. Our spatial atlas uncovers axes of resolution that are not apparent from single-cell RNA sequencing data – for example, in the gut tube we observe early dorsal-ventral separation of esophageal and tracheal progenitor populations. In sum, by computationally integrating high-resolution spatially-resolved gene expression maps with single-cell genomics data, we provide a powerful new approach for studying how and when cell fate decisions are made during early mammalian development.

Competing Interest Statement

W.R. is a consultant and shareholder of Cambridge Epigenetix. L.C. is the co-founder of Spatial Genomics Inc. and holds patents on seqFISH.

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 4.0 International license.
Back to top
PreviousNext
Posted November 21, 2020.
Download PDF

Supplementary Material

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.
Highly multiplexed spatially resolved gene expression profiling of mouse organogenesis
(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
Highly multiplexed spatially resolved gene expression profiling of mouse organogenesis
T. Lohoff, S. Ghazanfar, A. Missarova, N. Koulena, N. Pierson, J.A. Griffiths, E.S. Bardot, C.-H.L. Eng, R.C.V. Tyser, R. Argelaguet, C. Guibentif, S. Srinivas, J. Briscoe, B.D. Simons, A.-K. Hadjantonakis, B. Göttgens, W. Reik, J. Nichols, L. Cai, J.C. Marioni
bioRxiv 2020.11.20.391896; doi: https://doi.org/10.1101/2020.11.20.391896
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Highly multiplexed spatially resolved gene expression profiling of mouse organogenesis
T. Lohoff, S. Ghazanfar, A. Missarova, N. Koulena, N. Pierson, J.A. Griffiths, E.S. Bardot, C.-H.L. Eng, R.C.V. Tyser, R. Argelaguet, C. Guibentif, S. Srinivas, J. Briscoe, B.D. Simons, A.-K. Hadjantonakis, B. Göttgens, W. Reik, J. Nichols, L. Cai, J.C. Marioni
bioRxiv 2020.11.20.391896; doi: https://doi.org/10.1101/2020.11.20.391896

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

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4241)
  • Biochemistry (9173)
  • Bioengineering (6806)
  • Bioinformatics (24064)
  • Biophysics (12155)
  • Cancer Biology (9565)
  • Cell Biology (13825)
  • Clinical Trials (138)
  • Developmental Biology (7658)
  • Ecology (11737)
  • Epidemiology (2066)
  • Evolutionary Biology (15543)
  • Genetics (10672)
  • Genomics (14360)
  • Immunology (9512)
  • Microbiology (22903)
  • Molecular Biology (9129)
  • Neuroscience (49115)
  • Paleontology (357)
  • Pathology (1487)
  • Pharmacology and Toxicology (2583)
  • Physiology (3851)
  • Plant Biology (8351)
  • Scientific Communication and Education (1473)
  • Synthetic Biology (2301)
  • Systems Biology (6205)
  • Zoology (1302)