title: A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division.
abstract: 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.
authors.affiliation: Institut Pasteur, Stem Cells and Development, Department of Developmental Biology, CNRS URA 2578, 25 rue du Dr. Roux, Paris 75015, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rocheteau
authors.forename: Barbara
authors.initials: B
authors.lastname: Gayraud-Morel
authors.forename: Irene
authors.initials: I
authors.lastname: Siegl-Cachedenier
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002455:Cell Division; D020090:Chromosome Segregation; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D013698:Templates, Genetic
chemical_list: D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse