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| Item Type: | Article |
|---|---|
| Title: | Spatially resolved multiomics of human cardiac niches |
| Creators: |
Kanemaru, K., Cranley, J., Muraro, D., Miranda, A.M.A., Ho, S.Y., Wilbrey-Clark, A., Patrick Pett, J., Polanski, K., Richardson, L., Litvinukova, M.  ORCID: https://orcid.org/0000-0002-6713-3647, Kumasaka, R., Qin, Y., Jablonska, Z., Semprich, C.I., Mach, L., Dabrowska, M., Richoz, R., Bolt, L., Mamanova, L., Kapuge, R., Barnett, S.N., Perera, S., Talavera-López, C., Mulas, I., Mahbubani, K.T., Tuck, Liz, Wang, Lu, Huang, M.M., Prete, M., Pritchard, S., Dark, J., Saeb-Parsy, K., Patel, M., Clatworthy, M.R., Hübner, N. ORCID: https://orcid.org/0000-0002-1218-6223, Chowdhury, R.A., Noseda, M. and Teichmann, S.A.
|
| 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. |
| Keywords: | Cardiac Myocytes, Fibroblasts, Ion Channels, Multiomics, Sinoatrial Node |
| Source: | Nature |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Volume: | 619 |
| Page Range: | 801-810 |
| Date: | 27 July 2023 |
| Additional Information: | Erratum in Nature 640(8058):e4. |
| Official Publication: | https://doi.org/10.1038/s41586-023-06311-1 |
| PubMed: | View item in PubMed |
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