Journal Article

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

Missarova, A., Marioni, J. C., Koulena, N., Cai, L., Guibentif, C., Nichols, J., Ghazanfar, S., Bardot, E. S., Göttgens, B., Briscoe, J., Simons, B. D., Tyser, R. C. V., Srinivas, S., Hadjantonakis, A.-K., Pierson, N., Eng, C.-H. L., Argelaguet, R., Reik, W., Griffiths, J. A., Lohoff, T.

2022

Overview

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. Improved integration of spatial and single-cell transcriptomic data provides insights into mouse development.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/114 / 631/136/2086 / Agriculture / Animals / Bioinformatics / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biotechnology / Cell differentiation / Cell fate / Cell fate decision / Context / Cytology / Differentiation (biology) / Embryos / Esophagus / Fluorescence / Fluorescence in situ hybridization / Fluorescence microscopy / Gene expression / Gene sequencing / Genes / Hindbrain / Histology / In Situ Hybridization, Fluorescence - methods / Integration / Life Sciences / Medical Biotechnology / Medicinsk bioteknologi / Mesencephalon / Mice / Molecular basis / Molecular profiling / Organogenesis / Organogenesis - genetics / Plants (botany) / Population statistics / Regulatory process / RNA, Messenger - genetics / Single-Cell Analysis - methods / Spatially resolved / Target detection / Tissue / Tissue engineering / Tissue sections / Transcription / Transcriptome - genetics / Transcriptomes / Transcriptomics