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Spatially resolved multiomics of human cardiac niches

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Item Type:Article
Title:Spatially resolved multiomics of human cardiac niches
Creators Name:Kanemaru, K. and Cranley, J. and Muraro, D. and Miranda, A.M.A. and Ho, S.Y. and Wilbrey-Clark, A. and Patrick Pett, J. and Polanski, K. and Richardson, L. and Litvinukova, M. and Kumasaka, R. and Qin, Y. and Jablonska, Z. and Semprich, C.I. and Mach, L. and Dabrowska, M. and Richoz, R. and Bolt, L. and Mamanova, L. and Kapuge, R. and Barnett, S.N. and Perera, S. and Talavera-López, C. and Mulas, I. and Mahbubani, K.T. and Tuck, Liz and Wang, Lu and Huang, M.M. and Prete, M. and Pritchard, S. and Dark, J. and Saeb-Parsy, K. and Patel, M. and Clatworthy, M.R. and Hübner, N. and Chowdhury, R.A. and Noseda, M. and Teichmann, S.A.
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 system1. 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.
Keywords:Cardiac Myocytes, Fibroblasts, Ion Channels, Multiomics, Sinoatrial Node
Publisher:Nature Publishing Group
Page Range:801-810
Date:27 July 2023
Official Publication:https://doi.org/10.1038/s41586-023-06311-1
PubMed:View item in PubMed

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