학술논문
Spatially resolved multiomics of human cardiac niches
Document Type
Article
Author
Kanemaru, Kazumasa; Cranley, James; Muraro, Daniele; Miranda, Antonio M. A.; Ho, Siew Yen; Wilbrey-Clark, Anna; Patrick Pett, Jan; Polanski, Krzysztof; Richardson, Laura; Litvinukova, Monika; Kumasaka, Natsuhiko; Qin, Yue; Jablonska, Zuzanna; Semprich, Claudia I.; Mach, Lukas; Dabrowska, Monika; Richoz, Nathan; Bolt, Liam; Mamanova, Lira; Kapuge, Rakeshlal; Barnett, Sam N.; Perera, Shani; Talavera-López, Carlos; Mulas, Ilaria; Mahbubani, Krishnaa T.; Tuck, Liz; Wang, Lu; Huang, Margaret M.; Prete, Martin; Pritchard, Sophie; Dark, John; Saeb-Parsy, Kourosh; Patel, Minal; Clatworthy, Menna R.; Hübner, Norbert; Chowdhury, Rasheda A.; Noseda, Michela; Teichmann, Sarah A.
Source
Nature; July 2023, Vol. 619 Issue: 7971 p801-810, 10p
Subject
Language
ISSN
00280836; 14764687
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 FOXP2in 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.