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Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells

Nature Cell Biology volume 8, pages 677–682 (2006)Cite this article

Abstract

Satellite cells assure postnatal skeletal muscle growth and repair. Despite extensive studies, their stem cell character remains largely undefined. Using pulse-chase labelling with BrdU to mark the putative stem cell niche, we identify a subpopulation of label-retaining satellite cells during growth and after injury. Strikingly, some of these cells display selective template-DNA strand segregation during mitosis in the muscle fibre in vivo, as well as in culture independent of their niche, indicating that genomic DNA strands are nonequivalent. Furthermore, we demonstrate that the asymmetric cell-fate determinant Numb segregates selectively to one daughter cell during mitosis and before differentiation, suggesting that Numb is associated with self-renewal. Finally, we show that template DNA cosegregates with Numb in label-retaining cells that express the self-renewal marker Pax7. The cosegregation of 'immortal' template DNA strands and their link with the asymmetry apparatus has important implications for stem cell biology and cancer.

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Figure 1: Asymmetric segregation of Numb in non-differentiating satellite cells.
Figure 2: Label-retaining cells in skeletal muscle during growth and after injury.
Figure 3: Asymmetric segregation of template DNA strands in label-retaining cells.
Figure 4: Live imaging of template DNA segregation in label-retaining cells.
Figure 5: Template DNA strand segregation in dividing satellite cells in vivo.
Figure 6: Niche-independent template DNA strand segregation in cultured satellite cells.
Figure 7: Template DNA strands and Numb cosegregate to one daughter cell during mitosis.

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Acknowledgements

We thank C. Potten, T. Partridge, F. Schweisguth, W. Zhong, and members of the Tajbakhsh lab for helpful comments, G. Cossu, J. Epstein, B. Mateescu O. Puijalon and S. Soddu for reagents. We also thank S. Shorte, P. Roux, E. Perret and M. Marchand from the Pasteur Imaging Center for their support. This work was funded by grants from the Pasteur Institute, Association Française contre les Myopathies (AFM), Association pour la Recherche sur le Cancer (ARC), Pasteur GPH 'Cellules Souches' programme, MyoRes (EU Framework 6 project LSHG-CT-2004-511978) and EuroStemCell (EU Framework 6 project LHSB-CT-2003-503005).u

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  1. Department of Developmental Biology, Stem Cells and Development, Pasteur Institute, CNRS URA 2578, 25 rue du Dr. Roux, Paris, 75724, Cedex 15, France

    Vasily Shinin, Barbara Gayraud-Morel, Danielle Gomès & Shahragim Tajbakhsh

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Shinin, V., Gayraud-Morel, B., Gomès, D. et al. Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nat Cell Biol 8, 677–682 (2006). https://doi.org/10.1038/ncb1425

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