Journal
CELL
Volume 148, Issue 1-2, Pages 112-125Publisher
CELL PRESS
DOI: 10.1016/j.cell.2011.11.049
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Funding
- Conseil de la Region Ile-de-France
- MICINN
- European Union (EU)
- European Research Council (ERC)
- Lilly Foundation
- Korber European Research Award
- Institut Pasteur
- Association Recherche contre le Cancer
- Association Francaise contre le Myopathies
- Centre national de la recherche scientifique
- Agence Nationale de la Recherche [ANR-06-BLAN-0039]
- Optistem
- Fondation pour la Recherche Medicale
- Agence Nationale de la Recherche (ANR) [ANR-06-BLAN-0039] Funding Source: Agence Nationale de la Recherche (ANR)
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Satellite cells are adult skeletal muscle stem cells that are quiescent and constitute a poorly defined heterogeneous population. Using transgenic Tg:Pax7-nGFP mice, we show that Pax7-nGFP(Hi) cells are less primed for commitment and have a lower metabolic status and delayed first mitosis compared to Pax7-nGFP(Lo) cells. Pax7-nGFP(Hi) can give rise to Pax7-nGFP(Lo) cells after serial transplantations. Proliferating Pax7-nGFP(Hi) cells exhibit lower metabolic activity, and the majority performs asymmetric DNA segregation during cell division, wherein daughter cells retaining template DNA strands express stem cell markers. Using chromosome orientation-fluorescence in situ hybridization, we demonstrate that all chromatids segregate asymmetrically, whereas Pax7-nGFP(Lo) cells perform random DNA segregation. Therefore, quiescent Pax7-nGFP(Hi) cells represent a reversible dormant stem cell state, and during muscle regeneration, Pax7-nGFP(Hi) cells generate distinct daughter cell fates by asymmetrically segregating template DNA strands to the stem cell. These findings provide major insights into the biology of stem cells that segregate DNA asymmetrically.
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