[HTML][HTML] A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division

P Rocheteau, B Gayraud-Morel, I Siegl-Cachedenier… - Cell, 2012 - cell.com
P Rocheteau, B Gayraud-Morel, I Siegl-Cachedenier, MA Blasco, S Tajbakhsh
Cell, 2012cell.com
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 …
Summary
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-nGFPHi cells are less primed for commitment and have a lower metabolic status and delayed first mitosis compared to Pax7-nGFPLo cells. Pax7-nGFPHi can give rise to Pax7-nGFPLo cells after serial transplantations. Proliferating Pax7-nGFPHi 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-nGFPLo cells perform random DNA segregation. Therefore, quiescent Pax7-nGFPHi cells represent a reversible dormant stem cell state, and during muscle regeneration, Pax7-nGFPHi 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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