Cardiopedia-Ligand: a Ligand Stimulation Atlas for Cardiac Function and Transcriptional Response

Here, we establish Cardiopedia-Ligand, a comprehensive perturbation–function–transcriptome atlas generated by stimulating human cardiac organoids (hCOs) with 87 ligands targeting 98 cell-membrane receptors expressed in the human heart.

We developed an automated high-throughput pipeline enabling individualized contractility measurements and single-organoid mRNA-sequencing. We use this pipeline to define both recognized and previously unrecognized functional and transcriptional clusters, including inotropes, endothelin peptides, extracellular matrix regulators, and multiple inflammatory clusters. Clustering analysis, machine learning, and ‘fingerprinting’ of human heart failure biopsies revealed previously underappreciated similarities between ligands and an interferon-γ signaling signature driving heart failure with preserved ejection fraction (HFpEF).