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Spatially resolved multiomics of human cardiac niches.

Kazumasa KanemaruJames CranleyDaniele MuraroAntonio M A MirandaSiew Yen HoAnna Wilbrey-ClarkJan Patrick PettKrzysztof PolańskiLaura RichardsonMonika LitvinukovaNatushiko KumasakaYue QinZuzanna JablonskaClaudia I SemprichLukas MachMonika DabrowskaNathan RichozLiam BoltLira MamanovaRakeshlal KapugeSam N BarnettShani PereraCarlos Talavera-LópezIlaria MulasKrishnaa T A MahbubaniLiz TuckLu WangMargaret M HuangMartin PreteSophie PritchardJohn H DarkKourosh Saeb ParsyMinal PatelMenna R ClatworthyNorbert HübnerRasheda A ChowdhuryMichela NosedaSarah A Teichmann
Published in: Nature (2023)
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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