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Spatially resolved multiomics of human cardiac niches.

The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system 1 . The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interaction

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Spatially resolved multiomics of human cardiac niches.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Kanemaru K, Cranley J, Muraro D, Miranda AMA, Ho SY, Wilbrey-Clark A, Patrick Pett J, Polanski K, Richardson L, Litvinukova M, Kumasaka N, Qin Y, Jablonska Z, Semprich CI, Mach L, Dabrowska M, Richoz N, Bolt L, Mamanova L, Kapuge R, Barnett SN, Perera S, Talavera-López C, Mulas I, Mahbubani KT, Tuck L, Wang L, Huang MM, Prete M, Pritchard S, Dark J, Saeb-Parsy K, Patel M, Clatworthy MR, Hübner N, Chowdhury RA, Noseda M, Teichmann SA. (2023). Spatially resolved multiomics of human cardiac niches. Nature. PMID 37438528 · PMC10371870 · DOI 10.1038/s41586-023-06311-1
  • 证据类型：PRIMARY_RESEARCH
  • 主题：single-cell、multi-omics
  • 被引次数（采集时）：340
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/37438528)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system 1 . The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG + and IgA + plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.

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    Spatially resolved multiomics of human cardiac niches. · GeniOmics