Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis.
Springer Science and Business Media LLC
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Lohoff, T., Ghazanfar, S., Missarova, A., Koulena, N., Pierson, N., Griffiths, J., Bardot, E., et al. (2022). Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis.. Nat Biotechnol, 40 (1), 74-85. https://doi.org/10.1038/s41587-021-01006-2
Funder: EMBL International PhD Programme
Funder: Support from the Francis Crick Institute, which receives core funding from CRUK, the UK Medical Research Council, and the Wellcome Trust (all under FC001051).
Funder: Core support from the MRC and the Wellcome Trust to the Wellcome-MRC Cambridge Stem Cell Institute.
Funder: Paul G Allen Frontiers Foundation Discovery Center for Cell Lineage Tracing (grant UWSC10142).
Funder: Core funding from EMBL
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.
Article, /631/114, /631/136/2086, article
Wellcome Trust (105031/D/14/Z)
Wellcome Trust (203813/Z/16/Z)
Medical Research Council (MR/M008975/1)
Medical Research Council (MC_PC_17230)
Wellcome Trust (219478/Z/19/Z)
British Heart Foundation (FS/18/24/33424)
External DOI: https://doi.org/10.1038/s41587-021-01006-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333149