A Subpopulation of Adult Skeletal Muscle Stem Cells Retains All Template DNA Strands after Cell Division

被引：352

作者：

Rocheteau, Pierre ^{[1
]}

Gayraud-Morel, Barbara ^{[1
]}

Siegl-Cachedenier, Irene ^{[2
]}

Blasco, Maria A. ^{[2
]}

Tajbakhsh, Shahragim ^{[1
]}

机构：

[1] CNRS, Dept Dev Biol, Inst Pasteur Stem Cells & Dev, URA 2578, F-75015 Paris, France

[2] Spanish Natl Canc Ctr CNIO, Mol Oncol Programme, Telomeres & Telomerase Grp, Madrid 28029, Spain

来源：

CELL | 2012年 / 148卷 / 1-2期

基金：

欧洲研究理事会;

关键词：

SATELLITE CELLS; SELF-RENEWAL; SELECTIVE SEGREGATION; DISTINCT; PAX7; HETEROGENEITY; EXPRESSION; SPECIFICATION; PROGENITORS; QUIESCENT;

D O I：

10.1016/j.cell.2011.11.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：112 / 125

页数：14

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