12/11, LSBM Monday Seminar Series #24, Kazumasa Kanemaru, Single-cell and spatial multiomics of the human heart

Title: Single-cell and spatial multiomics of the human heart

Presenter: Kazumasa Kanemaru

Affiliation: Teichmann Lab, Cellular Genetics, Wellcome Sanger Institute




The function of a cell is defined by its intrinsic characteristics and niche. 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 using paired single-nucleus RNA and ATAC sequencing data. 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 compartmentalised, 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. We validate a direct action of GLP-1 using
human-induced pluripotent stem cell-derived cardiomyocytes (hiPCS-CM). In the
epicardium, we show enrichment of IgG+ and IgA+ plasma cells forming immune niches that
may contribute to infection defence. We define a ventricular myocardial-stress niche
enriched for activated fibroblasts and stressed cardiomyocytes, cell states that are expanded
in cardiomyopathies.
Overall, we provide a comprehensive map of the human heart and new clarity to
cardiac electro-anatomy and immunology. Our suite of computational approaches can be
applied to other tissues and organs.


Kanemaru K. and Cranley J. et al., Spatially resolved multiomics of human cardiac niches.
Nature, 2023


2016 年 筑波大学医学専門学群医学類 卒業
2016 年 筑波大学大学院人間総合科学研究科生命システム医学 博士課程修了(免疫学研究室、渋谷彰 教授)
2016 年 筑波大学医学医療系 - 助教
2020  Wellcome Sanger Institute, Cellular Genetics, Teichmann Lab - Post-
doctroral fellow