Spatially resolved multiomics of human cardiac niches

作者：Kazumasa Kanemaru, J. Cranley, D. Muraro, A. Miranda, J. P. Pett, Monika Litviňuková, N. Kumasaka, S. Ho, K. Polański, L. Richardson, L. Mach, Monika Dabrowska, N. Richoz, Sam N. Barnett, Shani Perera, A. Wilbrey-Clark, Carlos Talavera-López, I. Mulas, Krishnaa T. A. Mahbubani, L. Bolt, L. Mamanova, L. Tuck, Lu Wang, Margaret M. Huang, M. Prete, S. Pritchard, J. Dark, K. Saeb-Parsy, Minal J. Patel, M. Clatworthy, N. Hübner, R. Chowdhury, M. Noseda, Sarah A. Teichmann · 发表于：bioRxiv · 年份：2023 · DOI：10.1038/s41586-023-06311-1 · 被引用次数：333 · 研究领域：Biology、Medicine

Single-cell and spatial transcriptomic analysis of eight human heart tissues reveals the cellular profiles and tissue architecture of niches including the cardiac conduction system, and a new tool, drug2cell, identifies drug target expression. 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 pro...