High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy.
Document Type
Article
Publication Date
10-13-2020
Keywords
JMG
JAX Source
Circulation 2020 Oct 13; 142(15):1448-1463
Volume
142
Issue
15
First Page
1448
Last Page
1463
ISSN
1524-4539
PMID
32795101
DOI
https://doi.org/10.1161/circulationaha.119.045115
Grant
CA034196
Abstract
BACKGROUND: Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative effect of disparate cell populations on cardiac fibrosis, remain unclear.
METHODS: We developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome, the network of cells that forms the heart. This method was used to profile the cardiac cellular ecosystem in response to 2 weeks of continuous administration of angiotensin II, a profibrotic stimulus that drives pathological cardiac remodeling.
RESULTS: Our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations, Fibroblast-
CONCLUSIONS: These results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes that precede chronic cardiac fibrosis.
Recommended Citation
McLellan M,
Skelly D,
Dona M,
Squiers G,
Farrugia G,
Gaynor T,
Cohen C,
Pandey R,
Diep H,
Vinh A,
Rosenthal N,
Pinto A.
High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy. Circulation 2020 Oct 13; 142(15):1448-1463
Comments
We acknowledge the use of JAX Flow Cytometry Core, Microscopy Core, Surgical Services, Histology Service, and Single-Cell Biology Laboratory, and the Monash Micro Imaging facility at the Alfred Research Alliance for provision of microscopy instrumentation and training. The data used for the analyses described in this article were obtained from the Genotype-Tissue Expression Portal on February 21, 2019.