A spatiotemporal atlas of mouse gastrulation and early organogenesis to explore axial patterning and project in vitro models onto in vivo space

Affiliations

¹ Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK. Electronic address: ltgh2@cam.ac.uk.
² Epigenetics Programme, The Babraham Institute, Cambridge, UK.
³ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁴ Institute of Computer Science, Georg-August University Göttingen, Göttingen, Germany.
⁵ 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.
⁶ Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK.
⁷ Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK.
⁸ Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
⁹ Epigenetics Programme, The Babraham Institute, Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
¹⁰ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
¹¹ 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.
¹² Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK. Electronic address: bg200@cam.ac.uk.
¹³ 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. Electronic address: shila.ghazanfar@sydney.edu.au.

PMID: 40728928
DOI: 10.1016/j.celrep.2025.116047

Free article

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 et al. Cell Rep. 2025.

Free article

. 2025 Aug 26;44(8):116047.

doi: 10.1016/j.celrep.2025.116047. Epub 2025 Jul 28.

Authors

Affiliations

¹ Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Wolfson College, University of Cambridge, Cambridge, UK. Electronic address: ltgh2@cam.ac.uk.
² Epigenetics Programme, The Babraham Institute, Cambridge, UK.
³ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
⁴ Institute of Computer Science, Georg-August University Göttingen, Göttingen, Germany.
⁵ 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.
⁶ Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK.
⁷ Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK.
⁸ Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
⁹ Epigenetics Programme, The Babraham Institute, Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
¹⁰ MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.
¹¹ 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.
¹² Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK. Electronic address: bg200@cam.ac.uk.
¹³ 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. Electronic address: shila.ghazanfar@sydney.edu.au.

PMID: 40728928
DOI: 10.1016/j.celrep.2025.116047

Abstract

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.

Keywords: CP: Developmental biology; CP: Genomics; axial patterning; gastrulation; gastruloids; mouse development; organogenesis; single cell transcriptomics; spatial transcriptomics; spatiotemporal atlas.

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Conflict of interest statement

Declaration of interests T.L. is an employee of Forbion. J.G. and W.R. are employees of Altos Labs. W.R. is a consultant and shareholder of Biomodal. J.C.M. has been an employee of Genentech since September 2022. N.K. is an employee of Merck Co.

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A spatiotemporal atlas of mouse gastrulation and early organogenesis to explore axial patterning and project in vitro models onto in vivo space

Affiliations

A spatiotemporal atlas of mouse gastrulation and early organogenesis to explore axial patterning and project in vitro models onto in vivo space

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Miscellaneous