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

Pierre Rocheteau | Zendy; Barbara Gayraud-Morel | Zendy; Irene SieglCachedenier | Zendy; Marı́a A. Blasco | Zendy; Shahragim Tajbakhsh | Zendy

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

Author(s) -

Pierre Rocheteau,

Barbara Gayraud-Morel,

Irene SieglCachedenier,

Marı́a A. Blasco,

Shahragim Tajbakhsh

Publication year - 2012

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2011.11.049

Subject(s) - biology , stem cell , microbiology and biotechnology , cell division , mitosis , cellular differentiation , population , adult stem cell , cell , genetics , gene , demography , sociology

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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