Title

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

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.

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.

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