Browse by author
Lookup NU author(s): Dr Lu Wang, Professor John Dark
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).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.
Author(s): 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-Lopez C, Mulas I, Mahbubani KT, Tuck L, Wang L, Huang MM, Prete M, Pritchard S, Dark J, Saeb-Parsy K, Patel M, Clatworthy MR, Hubner N, Chowdhury RA, Noseda M, Teichmann SA
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2023
Volume: 619
Pages: 801-810
Online publication date: 12/07/2023
Acceptance date: 12/06/2023
Date deposited: 07/08/2023
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-023-06311-1
DOI: 10.1038/s41586-023-06311-1
Altmetrics provided by Altmetric
