Spatially resolved multiomics of human cardiac niches

Kazumasa Kanemaru, James Cranley, Daniele Muraro, Antonio M. A. Miranda, Siew Yen Ho, Anna Wilbrey-Clark, Jan Patrick Pett, Krzysztof Polanski, Laura Richardson, Monika Litvinukova, Natsuhiko Kumasaka, Yue Qin, Zuzanna Jablonska, Claudia I. Semprich, Lukas Mach, Monika Dabrowska, Nathan Richoz, Liam Bolt, Lira Mamanova, Rakeshlal Kapuge, Sam N. Barnett, Shani Perera, Carlos Talavera-López, Ilaria Mulas, Krishnaa T. Mahbubani, Liz Tuck, Lu Wang, Margaret M. Huang, Martin Prete, Sophie Pritchard, John Dark, Kourosh Saeb-Parsy, Minal Patel, Menna R. Clatworthy, Norbert Hübner, Rasheda A. Chowdhury, Michela Noseda () and Sarah A. Teichmann ()
Additional contact information
Kazumasa Kanemaru: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
James Cranley: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Daniele Muraro: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Antonio M. A. Miranda: Imperial College London
Siew Yen Ho: Royal Brompton Hospital and Imperial College London
Anna Wilbrey-Clark: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Jan Patrick Pett: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Krzysztof Polanski: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Laura Richardson: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Monika Litvinukova: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Natsuhiko Kumasaka: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Yue Qin: Imperial College London
Zuzanna Jablonska: Imperial College London
Claudia I. Semprich: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Lukas Mach: Imperial College London
Monika Dabrowska: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Nathan Richoz: University of Cambridge, MRC Laboratory of Molecular Biology
Liam Bolt: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Lira Mamanova: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Rakeshlal Kapuge: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Sam N. Barnett: Imperial College London
Shani Perera: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Carlos Talavera-López: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Ilaria Mulas: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Krishnaa T. Mahbubani: NIHR Cambridge Biomedical Centre
Liz Tuck: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Lu Wang: Newcastle University
Margaret M. Huang: NIHR Cambridge Biomedical Centre
Martin Prete: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Sophie Pritchard: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
John Dark: Newcastle University
Kourosh Saeb-Parsy: NIHR Cambridge Biomedical Centre
Minal Patel: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Menna R. Clatworthy: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton
Norbert Hübner: Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
Rasheda A. Chowdhury: Imperial College London
Michela Noseda: Imperial College London
Sarah A. Teichmann: Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton

Nature, 2023, vol. 619, issue 7971, 801-810

Abstract: 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.

Date: 2023
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Citations: View citations in EconPapers (11)

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DOI: 10.1038/s41586-023-06311-1

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