Asymmetric Division and Cosegregation of Template DNA Strands in Adult Muscle Satellite Cells

Nat Cell Biol. 2006 Jul;8(7):677-87. doi: 10.1038/ncb1425. Epub 2006 Jun 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine
  • Cell Lineage / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cells, Cultured
  • DNA Replication / physiology*
  • DNA, Single-Stranded / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Mitosis / physiology*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Regeneration / physiology*
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / metabolism*

Substances

  • DNA, Single-Stranded
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Numb protein, mouse
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Bromodeoxyuridine