Delta-Like 4 Activates Notch 3 to Regulate Self-Renewal in Skeletal Muscle Stem Cells.

Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a role for Notch3 (N3) in the self-renewal of muscle stem cells.

Skeletal muscle stem cells express anti-apoptotic ErbB receptors during activation from quiescence.

To be effective for tissue repair, satellite cells (the stem cells of adult muscle) must survive the initial activation from quiescence. Using an in vitro model of satellite cell activation, we show that erbB1, erbB2 and erbB3, members of the EGF receptor tyrosine kinase family, appear on satellite cells within 6 h of activation. We show that signalling via erbB2 provides an anti-apoptotic survival mechanism for satellite cells during the first 24 h, as they progress to a proliferative state.

Pax7 and myogenic progression in skeletal muscle satellite cells.

Skeletal muscle growth and regeneration are attributed to satellite cells - muscle stem cells resident beneath the basal lamina that surrounds each myofibre. Quiescent satellite cells express the transcription factor Pax7 and when activated, coexpress Pax7 with MyoD. Most then proliferate, downregulate Pax7 and differentiate.

Heparin-binding EGF-like growth factor shows transient left-right asymmetrical expression in mouse myotome pairs.

Heparin-binding EGF-like growth factor (HB-EGF) is a potent mitogen and chemoattractant for diverse cell types including, keratinocytes, fibroblasts and vascular smooth muscle cells. In adult mice, skeletal muscle and endothelial cells prominently express HB-EGF, although analysis of embryonic expression has been limited to studies of heart and kidney development. Here we survey HB-EGF mRNA expression in E7.

Mouse myotomes pairs exhibit left-right asymmetric expression of MLC3F and alpha-skeletal actin.

Most muscle originates from the myotomal compartment of the somites, paired structures flanking the neural tube. Whereas vertebrate embryos show molecular and morphological asymmetry about the left-right body axis, somitic myogenesis is thought to occur symmetrically. Here, we provide the first evidence that myotome pairs are transiently left-right asymmetric, with higher expression of alpha-skeletal actin and myosin light chain 3F (MLC3F) on the left side between embryonic day 9.

Role of interleukin-1beta in acute inflammation and graft death after cell transplantation to the heart.

Background: Poor survival of grafted cells is a major factor hindering the therapeutic effect of cell transplantation; however, the causes of cell death remain unclear. We hypothesized that interleukin-1beta (IL-1beta) might play a role in the acute inflammatory response and graft death after cell transplantation and that inhibition of IL-1beta might improve graft survival.

Methods And Results: 14C-labeled male skeletal muscle precursor cells were implanted into female mouse hearts by direct intramuscular injection.

Myf5 expression in satellite cells and spindles in adult muscle is controlled by separate genetic elements.

The myogenic regulatory factor Myf5 is integral to the initiation and control of skeletal muscle formation. In adult muscle, Myf5 is expressed in satellite cells, stem cells of mature muscle, but not in the myonuclei that sustain the myofibre. Using the Myf5(nlacZ/+) mouse, we now show that Myf5 is also constitutively expressed in muscle spindles-stretch-sensitive mechanoreceptors, while muscle denervation induces extensive reactivation of the Myf5 gene in myonuclei.

Muscle satellite cells adopt divergent fates: a mechanism for self-renewal?

Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates.

Dynamics and mediators of acute graft attrition after myoblast transplantation to the heart.

Survival and proliferation of skeletal myoblasts within the cardiac environment are crucial to the therapeutic efficacy of myoblast transplantation to the heart. We have analyzed the early dynamics of myoblasts implanted into the myocardium and investigated the mechanisms underlying graft attrition. At 10 min after implantation of [14C]thymidine-labeled male myoblasts into female mice hearts, 14C measurement showed that 39.

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium.

After myocardial infarction (MI), adverse remodeling with left ventricular (LV) dilatation is a major determinant of poor outcome. Skeletal myoblast (SkM) implantation improves cardiac function post-MI, although the mechanism is unclear. IL-1 influences post-MI hypertrophy and collagen turnover and is implicated in SkM death after grafting.

Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures.

Demonstration of the importance of the paired box transcription factor Pax7 for the murine myosatellite cell population, with persistent expression in mature skeletal muscle, prompted us to investigate the distribution of Pax7 protein in biopsy samples of normal and pathological human skeletal limb muscle. Immunostaining for M-cadherin, an adhesion molecule present at the interface between myofibre and satellite cell, and the characteristic position adjacent to the muscle fibre and beneath the fibre's basement membrane were used to identify satellite cells. Anti-Pax7 reactivity was found in the majority of satellite cells but a small population was Pax7 negative.

Kinetics of myoblast proliferation show that resident satellite cells are competent to fully regenerate skeletal muscle fibers.

The satellite cell compartment provides skeletal muscle with a remarkable capacity for regeneration. Here, we have used isolated myofibers to investigate the activation and proliferative potential of satellite cells. We have previously shown that satellite cells are heterogeneous: the majority express Myf5 and M-cadherin protein, presumably reflecting commitment to myogenesis, while a minority is negative for both.

Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site.

Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains.