Self-renewal and expansion of single transplanted muscle stem cells

By A. Sacco, R. Doyonnas, P. Kraft, S. Vitorovic, Helen M. Blau. Nature, 2008

854 citations recorded by the source corpus.

Adult muscle satellite cells have a principal role in postnatal skeletal muscle growth and regeneration. Satellite cells reside as quiescent cells underneath the basal lamina that surrounds muscle fibres and respond to damage by giving rise to transient amplifying cells (progenitors) and myoblasts that fuse with myofibres. Recent experiments showed that, in contrast to cultured myoblasts, satellite cells freshly isolated or satellite cells derived from the transplantation of one intact myofibre contribute robustly to muscle repair. However, because satellite cells are known to be heterogeneous, clonal analysis is required to demonstrate stem cell function. Here we show that when a single luciferase-expressing muscle stem cell is transplanted into the muscle of mice it is capable of extensive proliferation, contributes to muscle fibres, and Pax7+luciferase+ mononucleated cells can be readily re-isolated, providing evidence of muscle stem cell self-renewal. In addition, we show using in vivo bioluminescence imaging that the dynamics of muscle stem cell behaviour during muscle repair can be followed in a manner not possible using traditional retrospective histological analyses. By imaging luciferase activity, real-time quantitative and kinetic analyses show that donor-derived muscle stem cells proliferate and engraft rapidly after injection until homeostasis is reached. On injury, donor-derived mononucleated cells generate massive waves of cell proliferation. Together, these results show that the progeny of a single luciferase-expressing muscle stem cell can both self-renew and differentiate after transplantation in mice, providing new evidence at the clonal level that self-renewal is an autonomous property of a single adult muscle stem cell.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/071c675bf0a2c89e012c3b9b5b02dab015e7a5fa

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Citations in the corpus

Satellite Cells and Skeletal Muscle Regeneration (2015, positive): “In contrast to in vitro cultured myoblasts it has been shown that freshly isolated satellite cells (especially the satellite stem cell subpopulation) are capable of long-term engraftment and can sustain multiple round of injuries (51, 67, 163, 255).”
Satellite cells and the muscle stem cell niche. (2013, methodology): “Notably, the heterogeneity of gene expression in single satellite cells was investigated in a recent study, wherein the expression of Pax7, Pax3, Myf5, and MyoD was interrogated by RTqPCR for 40 individually FACS-isolated muscle stem cells (CD45 /CD11b /CD31 /Sca-1 / 7-intergin /CD34 ) (454).”
Tracking adult stem cells (2011, background): “The most stringent proof of stemness was provided when single, transplanted satellite cells repopulated new muscle fibres”
Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis (2011, background): “Satellite cells play important parts in skeletal muscle repai”
An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration (2011, background): “Because even a single Pax7+ cell can regenerate muscle efficiently after transplantation (Sacco et al., 2008), it is likely that bulk transplants of such preparations would favor a direct contribution to muscle regeneration from such contaminating Pax7+ cells.”
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle (2011, neutral): “1C) (Blanco-Bose et al., 2001; Rooney et al., 2009; Sacco et al., 2008).”
Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration (2011, background): “This contrasts with the demonstration that single fibres containing up to ~20 satellite cells, or even single cell transplantations, contribute considerably to muscle regeneration (Collins et al., 2005; Sacco et al., 2008).”
Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage (2012, background): “However, effective regeneration can occur following transplantation of only a few or even just one satellite cell (Collins et al., 2005; Sacco et al., 2008).”