Cells and gene expression programs in the adult human heart

Abstract

SummaryCardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease.

Benchmarking atlas-level data integration in single-cell genomics

“…scVI performed particularly well when the task contained complex batch effects (e.g., microwell-seq, single-cell and single-nuclei, or scATAC-seq data) and sufficient numbers of cells were present to fit these effects. Similar performance has been reported for another DL method, scGen 30 (not benchmarked here as it relies also on cell type information), on heart single-nucleus and single-cell data 31 . With more tunable parameters, these methods are more complex than other benchmarked methods and are more likely to require larger input data and hyperparameter optimization for optimal performance; however this also gives them the flexibility to fit complex batch effects.…”

A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease

“…These findings suggest MEOX1 functions as an essential transcriptional mediator of the FB to myoFB switch associated with fibrotic disease. Finally, using recently publicly available single cell data from the human adult heart (www.heartcellatlas.org) 29 , we found that MEOX1 was specifically expressed together with POSTN in a subset of activated FBs (Fig. 4G).…”

“…2H and Extended data Fig. 4A), a homeodomain-containing TF that is expressed in paraxial mesoderm and is required for sclerotome development 29,30 . Meox1 was particularly interesting because it was minimally expressed in the healthy mouse heart but highly upregulated in MyoFBs following TAC ( Fig.…”

A single-cell RNA expression map of human coronavirus entry factors

“…Severe heart damage and abnormal blood clotting has been reported in a substantial fraction of COVID-19 patients Wang et al, 2020a). We and others (Litviňuková et al, 2020) found that ACE2 is expressed in cardiomyocytes, but the same cell population does not appear to express TMPRSS2/4, so it remains unclear how the virus could infiltrate cardiomyocytes. Nonetheless, we observe that FURIN was co-expressed with ACE2 in a very small fraction (<0.1%) of cardiomyocytes.…”