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Myf5-Positive Satellite Cells Contribute to Pax7-Dependent Long-Term Maintenance of Adult Muscle Stem Cells

Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
Cell stem cell (Impact Factor: 22.15). 08/2013; 13(6). DOI: 10.1016/j.stem.2013.07.016
Source: PubMed

ABSTRACT Skeletal muscle contains Pax7-expressing muscle stem or satellite cells, enabling muscle regeneration throughout most of adult life. Here, we demonstrate that induced inactivation of Pax7 in Pax7-expressing cells of adult mice leads to loss of muscle stem cells and reduced heterochromatin condensation in rare surviving satellite cells. Inactivation of Pax7 in Myf5-expressing cells revealed that the majority of adult muscle stem cells originate from myogenic lineages, which express the myogenic regulators Myf5 or MyoD. Likewise, the majority of muscle stem cells are replenished from Myf5-expressing myogenic cells during adult life, and inactivation of Pax7 in Myf5-expressing cells after muscle damage leads to a complete arrest of muscle regeneration. Finally, we demonstrate that a relatively small number of muscle stem cells are sufficient for efficient repair of skeletal muscles. We conclude that Pax7 acts at different levels in a nonhierarchical regulatory network controlling muscle-satellite-cell-mediated muscle regeneration.

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Available from: Chen Ming Fan, Apr 03, 2014
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    • "The anti-apoptotic properties of Pax7 cannot be compensated by the closely related Pax3 protein, highlighting the importance of Pax7 in promoting cell survival and in controlling the stem cell populations of adult tissues (Relaix et al., 2006). More recent tissue-specific analyses have provided additional evidence for Pax7 function in the maintenance and regenerative capacity of satellite cells (Gunther et al., 2013; von Maltzahn et al., 2013). The onset of satellite cell differentiation leads to the down-regulation of Pax7 and triggers the expression of myogenin (Zammit et al., 2004). "
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    • "During CTX-induced regeneration in control mice, protein expression of Pax7, a definitive satellite cell marker [24] [25], is highly induced at day 5 with substantially higher levels still detected at day 8 (Fig. 6A), suggesting a marked increase of the satellite cell pool during the peak of regenerative myogenesis, as documented previously [22] [23]. In contrast, this Pax7 response reflecting satellite cell expansion is severely blunted in Bmal1-null, with only slight induction at day 5 and weakly detectable levels at day 8. Analysis of Pax7 transcripts revealed significantly lower levels in Bmal1 -/-mice throughout injury as compared to the WT (Fig. 6B). "
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    • "During CTX-induced regeneration in control mice, protein expression of Pax7, a definitive satellite cell marker [24] [25], is highly induced at day 5 with substantially higher levels still detected at day 8 (Fig. 6A), suggesting a marked increase of the satellite cell pool during the peak of regenerative myogenesis, as documented previously [22] [23]. In contrast, this Pax7 response reflecting satellite cell expansion is severely blunted in Bmal1-null, with only slight induction at day 5 and weakly detectable levels at day 8. Analysis of Pax7 transcripts revealed significantly lower levels in Bmal1 -/-mice throughout injury as compared to the WT (Fig. 6B). "
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