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Updated: Dec 20, 2025

Isolation and Characterization of Adult Cardiac Fibroblasts and Myofibroblasts
Published on: March 12, 2020
Cardiac fibroblast diversity in health and disease
Hesham Soliman1, Fabio M V Rossi2
1Biomedical Research Centre, University of British Columbia, Vancouver, Canada; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T1Z3, Canada; Faculty of Pharmacy, Minia University, Minia, Egypt.
Insights
Cardiac fibroblasts exhibit significant diversity, with single-cell sequencing revealing a differentiation cascade. This heterogeneity influences the heart
Area of Science:
- Cardiovascular Biology
- Cellular Heterogeneity
- Fibroblast Biology
Background:
- The cardiac stroma, particularly fibroblasts, is crucial for extracellular matrix regulation in the heart.
- Fibroblast heterogeneity has been recognized but poorly understood.
- Advancements in high-throughput methods are enhancing our understanding of this cellular diversity.
Purpose of the Study:
- To explore the diversity of cardiac fibroblasts and their progenitors.
- To highlight new insights from single-cell sequencing and fate mapping studies.
- To compare stromal responses to damage in cardiac versus skeletal muscle.
Main Methods:
- Single-cell sequencing
- Fate mapping studies
- Comparative analysis of organ-specific stromal responses
Main Results:
- Cardiac fibroblasts display significant heterogeneity, suggesting a differentiation cascade.
- Stromal responses to damage differ between non-regenerating (heart) and regenerating (skeletal muscle) organs.
- Fibroblasts share properties across organs but possess distinct organ-specific transcriptional signatures and differentiation biases.
Conclusions:
- Cardiac fibroblast heterogeneity is substantial and linked to differentiation pathways.
- Organ-specific characteristics of stromal cells contribute to differential responses to injury.
- Understanding fibroblast diversity is key to addressing cardiac damage and disease.
Abstract:
The cardiac stroma plays essential roles in health and following cardiac damage. The major player of the stroma with respect to extracellular matrix deposition, maintenance and remodeling is the poorly defined fibroblast. It has long been recognized that there is considerable variability to the fibroblast phenotype. With the advent of new, high throughput analytical methods our understanding and appreciation of this heterogeneity has grown dramatically. This review aims to explore the diversity of cardiac fibroblasts and highlights new insights into the diverse nature of these cells and their progenitors as revealed by single cell sequencing and fate mapping studies. We propose that at least in part the observed heterogeneity is related to the existence of a differentiation cascade within stromal cells. Beyond in-organ heterogeneity, we also discuss how the stromal response to damage differs between non-regenerating organs such as the heart and regenerating organs such as skeletal muscle. In exploring possible causes for these differences, we outline that although fibrogenic cells from different organs overlap in many properties, they still possess organ-specific transcriptional signatures and differentiation biases that make them functionally distinct.

