A spatiotemporal atlas of mouse gastrulation and early organogenesis to explore axial patterning and project in vitro models onto in vivo space
Luke T.G. Harland,
Tim Lohoff,
Noushin Koulena,
Nico Pierson,
Constantin Pape,
Farhan Ameen,
Jonathan Griffiths,
Bart Theeuwes,
Nicola K. Wilson,
Anna Kreshuk,
Wolf Reik,
Jennifer Nichols,
Long Cai,
John C. Marioni,
Berthold Göttgens,
Shila Ghazanfar
Affiliations
Luke T.G. Harland
Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK; Corresponding author
Tim Lohoff
Epigenetics Programme, The Babraham Institute, Cambridge, UK
Noushin Koulena
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Nico Pierson
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Constantin Pape
Institute of Computer Science, Georg-August University Göttingen, Göttingen, Germany
Farhan Ameen
School of Mathematics and Statistics, The University of Sydney, Camperdown, NSW, Australia; Sydney Precision Data Science Centre, The University of Sydney, Camperdown, NSW, Australia; Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
Jonathan Griffiths
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
Bart Theeuwes
Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK
Nicola K. Wilson
Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK
Anna Kreshuk
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
Wolf Reik
Epigenetics Programme, The Babraham Institute, Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Jennifer Nichols
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
Long Cai
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
John C. Marioni
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Berthold Göttgens
Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Corresponding author
Shila Ghazanfar
School of Mathematics and Statistics, The University of Sydney, Camperdown, NSW, Australia; Sydney Precision Data Science Centre, The University of Sydney, Camperdown, NSW, Australia; Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia; Corresponding author
Summary: During gastrulation, mouse epiblast cells form the three germ layers that establish the body plan and initiate organogenesis. While single-cell atlases have advanced our understanding of lineage diversification, spatial aspects of differentiation remain poorly defined. Here, we applied spatial transcriptomics to mouse embryos at embryonic (E) E7.25 and E7.5 days and integrated these data with existing E8.5 spatial and E6.5–E9.5 single-cell RNA-seq atlases. This resulted in a spatiotemporal atlas of over 150,000 cells with 82 refined cell-type annotations. The resource enables exploration of gene expression dynamics across anterior-posterior and dorsal-ventral axes, uncovering spatial logic guiding mesodermal fate decisions in the primitive streak. We also developed a computational pipeline to project additional single-cell datasets into this framework for comparative analysis. Freely accessible through an interactive web portal, this atlas offers a valuable tool for the developmental and stem cell biology communities to investigate mouse embryogenesis in a spatial and temporal context.
