Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis.

Autor: Lohoff T; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Epigenetics Programme, Babraham Institute, Cambridge, UK., Ghazanfar S; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Missarova A; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK., Koulena N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Pierson N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Griffiths JA; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.; Genomics Plc, Cambridge, UK., Bardot ES; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Eng CL; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA., Tyser RCV; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Argelaguet R; Epigenetics Programme, Babraham Institute, Cambridge, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK., Guibentif C; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK.; Sahlgrenska Center for Cancer Research, Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden., Srinivas S; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK., Briscoe J; The Francis Crick Institute, London, UK., Simons BD; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; The Wellcome/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.; Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Cambridge, UK., Hadjantonakis AK; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Göttgens B; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.; Department of Haematology, University of Cambridge, Cambridge, UK., Reik W; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. wolf.reik@babraham.ac.uk.; Epigenetics Programme, Babraham Institute, Cambridge, UK. wolf.reik@babraham.ac.uk.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. wolf.reik@babraham.ac.uk.; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. wolf.reik@babraham.ac.uk., Nichols J; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. jn270@cam.ac.uk.; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. jn270@cam.ac.uk., Cai L; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. lcai@caltech.edu., Marioni JC; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. marioni@ebi.ac.uk.; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK. marioni@ebi.ac.uk.; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. marioni@ebi.ac.uk.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2022 Jan; Vol. 40 (1), pp. 74-85. Date of Electronic Publication: 2021 Sep 06.
DOI: 10.1038/s41587-021-01006-2
Abstrakt: Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8-12 somite stage. By integrating spatial context and multiplexed transcriptional measurements with two single-cell transcriptome atlases, we characterize cell types across the embryo and demonstrate that 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 (MHB) and the developing gut tube. We uncover axes of cell differentiation that are not apparent from single-cell RNA-sequencing (scRNA-seq) data, such as early dorsal-ventral separation of esophageal and tracheal progenitor populations in the gut tube. Our method provides an approach for studying cell fate decisions in complex tissues and development.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: