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.