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

Abstract:
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.

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

略歴
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 年 Wellcome　Sanger　Institute,　Cellular　Genetics,　Teichmann　Lab　-　Post-
doctroral　fellow