Résumé :
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Muscle satellite cells are mitotically quiescent in adult muscle but are activated immediately following muscle injury. Activated satellite cells proliferate and differentiate for supplying myonuclei, and also self-renew for maintaining satellite cell pool. Fast-dividing and slow-dividing cell populations in activated satellite cells have been observed, but the biological roles of these cells are unclear. Here, we undertook to elucidate the relation between proliferation behavior and stem cell function of these cells. To assess the frequency of cell division, satellite cells isolated from EDL in mice was labeled with a fluorescent lipophilic dye PKH26. Time-lapse analysis revealed that a small population retaining high level of PKH26 dye existed even under the growth culture-condition. Both of fast-dividing PKH26low and slow-dividing PKH26high populations sorted by FACS underwent myogenic differentiation and produced self-renewed cells, but only PKH26high population was able to give rise to extensively proliferative progeny having long-term self-renewal capacity when repeated passages. Id1 protein, a negative regulator for bHLH transcriptional factors, was expressed in all activated satellite cells, but the expression level was varied even within PKH26high population. We further characterized that the long-term self-renewable population was restricted to a compartment that expresses high level of Id1 protein (PKH26high/Id1high population). Genome-wide gene expression analysis identified the molecular characteristics of PKH26high/Id1high population. Taken together, our results indicate that slow-dividing population expressing high level of Id1 protein in activated satellite cells retains long-term self-renewal ability, and so PKH26high/Id1high population may be essential for efficient repeated regeneration of adult muscle.
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