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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
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Controlling cardiac fibrosis through fibroblast state space modulation
Isabella M Reichardt1, Kalen Z Robeson1, Michael Regnier2
1Department of Bioengineering, University of Washington, Seattle, WA 98105, United States.
Cellular Signalling
|December 19, 2020
Summary
Cardiac fibroblasts transition into myofibroblasts through complex, dynamic cell states, not a simple linear path. Understanding this cellular state space offers new therapeutic targets for cardiac fibrosis.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Fibrosis Research
Background:
- Cardiac fibroblasts traditionally transform unidirectionally into myofibroblasts post-injury.
- Recent studies reveal fibroblast heterogeneity and complex transdifferentiation pathways.
- Existing models do not fully capture the dynamic nature of fibroblast states.
Purpose of the Study:
- To re-examine cardiac fibroblast transdifferentiation using a dynamic state space model.
- To explore how fibroblast state dynamics influence cardiac fibrotic remodeling.
- To identify therapeutic strategies targeting fibroblast states in cardiac fibrosis.
Main Methods:
- Review of lineage tracing and single-cell RNA sequencing data.
- Analysis of canonical and non-canonical fibrotic signaling pathways.
- Exploration of therapeutic interventions modulating fibroblast state space.
Main Results:
- Fibroblast transdifferentiation is a complex process involving multiple cell states.
- Fibroblast state dynamics significantly impact cardiac fibrotic remodeling.
- Signaling pathways critically modulate fibroblast cell states and fibrosis.
Conclusions:
- A dynamic state space lens provides a more comprehensive understanding of fibroblast behavior.
- Targeting fibroblast state modulation offers potential therapeutic avenues for cardiac fibrosis.
- Interventions like p38 and YAP inhibition show promise in fibroblast reprogramming.
