Mapping the cardiac vascular niche in heart failure

• Published in: Nature communications Vol. 13; no. 1; pp. 3027 - 20
• Main Authors: Peisker, Fabian, Halder, Maurice, Nagai, James, Ziegler, Susanne, Kaesler, Nadine, Hoeft, Konrad, Li, Ronghui, Bindels, Eric M. J., Kuppe, Christoph, Moellmann, Julia, Lehrke, Michael, Stoppe, Christian, Schaub, Michael T., Schneider, Rebekka K., Costa, Ivan, Kramann, Rafael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 14/1; 14/19; 38/88; 38/91; 631/1647/514/1949; 631/337/2019; 631/80/304; 692/4019/592/1540; 692/4019/592/75/230; Angiogenesis; Cell activation; Congestive heart failure; Endothelial cells; Endothelial Cells - metabolism; Fibroblasts; Fibroblasts - metabolism; Fibrosis; Gene mapping; Gene sequencing; Heart failure; Heart Failure - genetics; Heart Failure - metabolism; Heterogeneity; Homeostasis; Humanities and Social Sciences; Humans; Hypoxia; Injury prevention; multidisciplinary; Muscles; Myocytes, Smooth Muscle - metabolism; Niches; Pericytes - metabolism; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Smooth muscle; Tracing; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30682-0

The cardiac vascular and perivascular niche are of major importance in homeostasis and during disease, but we lack a complete understanding of its cellular heterogeneity and alteration in response to injury as a major driver of heart failure. Using combined genetic fate tracing with confocal imaging and single-cell RNA sequencing of this niche in homeostasis and during heart failure, we unravel cell type specific transcriptomic changes in fibroblast, endothelial, pericyte and vascular smooth muscle cell subtypes. We characterize a specific fibroblast subpopulation that exists during homeostasis, acquires Thbs4 expression and expands after injury driving cardiac fibrosis, and identify the transcription factor TEAD1 as a regulator of fibroblast activation. Endothelial cells display a proliferative response after injury, which is not sustained in later remodeling, together with transcriptional changes related to hypoxia, angiogenesis, and migration. Collectively, our data provides an extensive resource of transcriptomic changes in the vascular niche in hypertrophic cardiac remodeling. The cardiac vascular niche is of major importance in homeostasis and disease, but knowledge of its complexity in response to injury remains limited. Here we combine lineage tracing with single cell RNA sequencing to show alterations in fibroblasts, endothelial and mural cells in hypertrophic remodeling.