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Identifying regulators of aged fibroblast activation in 3D tissue models
Hui Liu1,2, Luezhen Yuan1,2,3, G V Shivashankar4,5
1Division of Biology and Chemistry, Paul Scherrer Institut, 5232, Villigen, Switzerland.
Scientific Reports
|November 26, 2025
Summary
Researchers identified key regulators of aged fibroblast activation using a novel bioinformatic pipeline. This work advances cell-based therapies and regenerative medicine by understanding fibroblast rejuvenation.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Regenerative Medicine
Background:
- Aged fibroblasts hinder effective cell-based therapies.
- Current methods lack robust 3D tissue models for activating aged fibroblasts.
- Compressive force activates aged fibroblasts, enhancing migration.
Purpose of the Study:
- To develop a pipeline for identifying regulators of aged fibroblast activation.
- To evaluate pharmacological inhibitors for transcription factor inference and cell migration.
- To discover master regulators for fibroblast rejuvenation and cell-based therapies.
Main Methods:
- RNA sequencing (RNA-seq) data integration with bioinformatic tools (prize collecting Steiner tree, iRegulon).
- Development of a pipeline for transcription factor inference.
- Validation using cell migration and heterochromatin content assays.
Main Results:
- Inferred 15 candidate regulators of aged fibroblast activation.
- Identified three potential master regulators: FOXO1, STAT3, and PDK1.
- Validated candidates through cell migration and heterochromatin assays.
Conclusions:
- FOXO1, STAT3, and PDK1 are key regulators of aged fibroblast activation and rejuvenation.
- The developed pipeline aids in identifying therapeutic targets.
- Findings support advancements in drug discovery, disease modeling, and regenerative medicine.
