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The circadian molecular clock creates epidermal stem cell heterogeneity
Peggy Janich1, Gloria Pascual, Anna Merlos-Suárez
1Center for Genomic Regulation and UPF, 08003 Barcelona, Spain.
Nature
|November 15, 2011
Summary
The circadian clock regulates epidermal stem cell activation. Disrupting this clock causes stem cell imbalance, leading to premature aging and altered tumor development.
Area of Science:
- Stem cell biology
- Chronobiology
- Dermatology
Background:
- Murine epidermal stem cells exhibit cycles of dormancy and activation for tissue renewal.
- Stem cell activation is heterogeneous, with cells in distinct responsive states.
- The hair-follicle stem cell niche harbors cells in opposing circadian phases.
Purpose of the Study:
- To investigate the role of the circadian clock in regulating epidermal stem cell heterogeneity and response to homeostatic cues.
- To determine how core clock proteins influence stem cell activation states.
- To assess the impact of circadian clock disruption on epidermal homeostasis and tumorigenesis.
Main Methods:
- Utilized a circadian-clock reporter-mouse model.
- Analyzed stem cell populations in the hair-follicle niche.
- Investigated gene expression modulation by the core clock protein Bmal1.
- Examined effects of deleting Bmal1 (Arntl) or Per1/2 genes.
Main Results:
- Coexisting stem cell populations in opposite circadian phases were identified in the dormant niche.
- Bmal1 expression oscillated, creating populations predisposed or less prone to activation.
- Deletion of Bmal1 or Per1/2 led to stem cell accumulation or depletion, respectively.
- Circadian disruption caused premature epidermal aging and reduced squamous tumor development.
Conclusions:
- The circadian clock precisely controls epidermal stem cell temporal behavior.
- Perturbation of the circadian clock disrupts stem cell homeostasis.
- Circadian clock equilibrium is critical for regulating tumorigenesis predisposition.
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