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Uncovering intestinal macrophages through the integration of single-cell and spatial transcriptomics

Genes & Immunity (2023)Cite this article

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Single-cell RNA sequencing (scRNA-seq) has expanded our understanding of a tissue’s cellular composition and provided the biomedical field with an invaluable tool to map disease-associated patterns at a resolution previously unattainable [1]. Furthermore, single-cell transcriptomics has enabled the discovery of dynamic and transitional cell states, challenging the traditional notion of discrete cell populations. One of the revelations of applying single-cell transcriptomics to tissue analysis has been the degree of heterogeneity that exists within cell lineages in both health and disease. Nonetheless, scRNA-seq has also brought with it certain challenges, including the difficulty of achieving consensus in cell type annotations, both within the same tissue and across different tissues, which can limit cross-study validation. In addition, the interpretation of scRNA-seq data has limitations; while the transcriptional profile of a cell reflects its lineage and state, it may not be enough to infer its function in a specific tissue or disease context.

Many possibilities remain ahead. For instance, spatial transcriptomics data could not only potentially support the identification of tissue neighborhoods with likely pathological implications, but also reveal key cell-to-cell and receptor-to-ligand interactions that could drive the development of novel therapeutic targets. Both applications require the development of the appropriate computational tools, some of which are now becoming available. In addition, spatial transcriptomics (especially when gene panels are custom made by users based on the specificities of the tissue at hand) can support direct cellular annotation, which could yield spatial information for further annotation of cell types. Such progress will provide an additional layer of information, potentially facilitating a consensus on their annotations.

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Fig. 1: Integration of single-cell RNA sequencing with cutting-edge spatial transcriptomics can provide a better understanding of cell types and cell functions in both healthy and diseased tissues.

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Authors and Affiliations

  1. Inflammatory Bowel Disease Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain

    Alba Garrido-Trigo, Marisol Veny & Azucena Salas

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

    Alba Garrido-Trigo, Marisol Veny & Azucena Salas

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  1. Alba Garrido-Trigo
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  2. Marisol Veny
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  3. Azucena Salas
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AG-T, MV and AS wrote and reviewed the manuscript. AG-T did the figure.

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Correspondence to Azucena Salas.

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Garrido-Trigo, A., Veny, M. & Salas, A. Uncovering intestinal macrophages through the integration of single-cell and spatial transcriptomics. Genes Immun (2023). https://doi.org/10.1038/s41435-023-00242-7

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