Rechercher des projets européens

Spatiotemporal regulation of epidermal stem cells by circadian rhythms: impact on homeostasis and aging (STEMCLOCK)
Date du début: 1 janv. 2013, Date de fin: 31 déc. 2017 PROJET  TERMINÉ 

"Most adult stem cells are compartmentalized in functionally deterministic niches where they self-renew and maintain homeostasis. From there, stem cells are instructed by combinations of signals and spatial tensile forces which they translate into a specific behavior. However how stem cells spatiotemporally coordinate their stem cell potential with niche- and systemic cues is poorly understood. These issues are essential since perturbations in stem cell function can cause tissue malfunction, such as tumorigenesis and aging.We propose to perform a systematic analysis to identify the molecular causes that underlie epidermal stem cell aging. We will focus on the interplay between circadian rhythms and stem cell function. The circadian machinery anticipates and synchronizes the daily function of tissues according to the entrainment by natural changes in light and metabolism. We have shown that the molecular clock fine-tunes the behavior of epidermal stem cells by imposing oscillations in the expression of stem cell regulatory genes. These oscillations provide stem cells with a spatiotemporal axis for responding to dormancy, activating, and differentiation cues. Notably, the stem cell clock is naturally dampened upon aging, and forced circadian arrhythmia causes severe epidermal aging and predisposition to tumorigenesis.We now propose to understand how the circadian clock coordinates the communication between stem cells with local and systemic cues, and how these are perturbed during aging. Specifically we aim: i) To study whether circadian rhythms coordinate the function of niche cells and epidermal stem cells; ii) To identify the molecular causes underlying the age-related dampening of the stem cell clock. We will combine large-scale genomic data, mouse models of circadian arrhythmia, and bioinformatic analysis. We hope to unveil some of the molecular causes underlying the loss of communication between epidermal stem cells and their environment resulting in aging."


2 Participants partenaires