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Updated: Aug 4, 2025

Establishing a High Throughput Epidermal Spheroid Culture System to Model Keratinocyte Stem Cell Plasticity
Published on: January 30, 2021
PGC-1s shape epidermal physiology by modulating keratinocyte proliferation and terminal differentiation
Simon-Pierre Gravel1,2,3, Youcef Ben Khalifa4, Shawn McGuirk1,2
1Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1) proteins are crucial for skin health and aging. Targeting PGC-1s shows potential for treating skin conditions and age-related changes.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Skin aging involves significant functional changes.
- Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1) family members regulate tissue biology.
- The role of PGC-1s in skin physiology is largely unknown.
Purpose of the Study:
- To investigate the role of PGC-1s in skin functions.
- To identify key substrates and regulators of PGC-1s in keratinocytes.
- To explore the potential of targeting PGC-1s for skin health.
Main Methods:
- Global gene expression profiling in keratinocytes.
- Gene silencing techniques to assess PGC-1 function.
- Analysis of reconstructed human epidermal equivalents.
- Assessment of mitochondrial respiration and keratinocyte proliferation.
Main Results:
- PGC-1s regulate metabolic genes and terminal differentiation programs in keratinocytes.
- Glutamine promotes mitochondrial respiration and keratinocyte proliferation, upregulating PGC-1s.
- Silencing PGC-1s decreased epidermal thickness.
- Salicylic acid derivatives enhanced PGC-1 expression and mitochondrial respiration.
Conclusions:
- PGC-1s are essential for epidermal physiology and function.
- The PGC-1 axis is a potential target for managing skin aging and conditions.
- Glutamine and salicylic acid derivatives influence PGC-1 activity and skin health.
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