Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure
Andrew L. Koenig, Irina Shchukina, Junedh Amrute, Prabhakar S. Andhey, Konstantin Zaitsev, Lulu Lai, Geetika Bajpai, Andrea Bredemeyer, Gabriella Smith, Cameran Jones, Emily Terrebonne, Stacey Rentschler, Maxim N. Artyomov, Kory J. Lavine
Abstract
Heart failure represents a major cause of morbidity and mortality worldwide. Single-cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression. Through integrated analysis of single-cell and single-nucleus RNA-sequencing data generated from 27 healthy donors and 18 individuals with dilated cardiomyopathy, here we define the cell composition of the healthy and failing human heart. We identify cell-specific transcriptional signatures associated with age and heart failure and reveal the emergence of disease-associated cell states. Notably, cardiomyocytes converge toward common disease-associated cell states, whereas fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type-specific transcriptional programs and disease-associated cell states and establish a valuable resource for the investigation of human heart failure.