Spatially resolved multiomics of human cardiac niches
File(s)
Published version
Author(s)
Type
Journal Article
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 Issued
2023-07-27
Date Acceptance
2023-06-12
Citation
Nature, 2023, 619 (7971), pp.801-810
ISSN
0028-0836
Publisher
Nature Research
Start Page
801
End Page
810
Journal / Book Title
Nature
Volume
619
Issue
7971
Copyright Statement
© 2023 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37438528
PII: 10.1038/s41586-023-06311-1
Subjects
Cell Communication
Cellular Microenvironment
Fibroblasts
Glutamic Acid
Heart
Heart Conduction System
Humans
Ion Channels
Multiomics
Myocardium
Myocytes, Cardiac
Neuroglia
Pericardium
Plasma Cells
Receptors, G-Protein-Coupled
Sinoatrial Node
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2023-07-12