{"id":"doi:10.1038/s41586-023-06311-1","kind":"article","title":"Spatially resolved multiomics of human cardiac niches","authors":["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"],"author_count":38,"year":2023,"published":"2023-07-12","venue":"Nature","cited_by":413,"doi":"10.1038/s41586-023-06311-1","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41586-023-06311-1","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41586-023-06311-1","updated":null,"pmid":"37438528","pmcid":"PMC10371870","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10371870/pdf","abstract":"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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Spatially resolved multiomics of human cardiac niches\" by Kanemaru K, Cranley J, Muraro D et al., https://doi.org/10.1038/s41586-023-06311-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}