A Temporal Switch from Notch to Wnt Signaling in Muscle Stem Cells Is Necessary for Normal Adult Myogenesis

Brack, Andrew S.; Conboy, Irina M.; Conboy, Michael J.; Shen, Jeanne; Rando, Thomas A.

doi:10.1016/j.stem.2007.10.006

Cited by 561 publications

(633 citation statements)

References 36 publications

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“…For example, activation of the noncanonical WNT/ planar cell polarity pathway promotes the expansion of satellite cells by stimulating symmetric cell divisions to produce two daughter satellite cells during the self-renewal process (36). By contrast, injury-induced muscle regeneration results in canonical WNT/β-catenin pathway activation and myogenic differentiation of satellite cells (18). These studies suggest that canonical and noncanonical pathways play antagonistic roles in regulating satellite cell function.…”

Section: Discussionmentioning

confidence: 99%

“…Additional molecular pathways that regulate satellite cell self-renewal also have important roles in ERMS. For example, the Notch pathway promotes activation and proliferation of satellite cells during regeneration (18). In human ERMS cells, knockdown of the Notch1-Hey1 axis or Notch3 resulted in reduced tumor cell growth and enhanced myogenic differentiation (37,38), suggesting that the Notch pathway may regulate self-renewal and differentiation of human ERMS.…”

Section: Discussionmentioning

confidence: 99%

“…Because canonical WNT/ β-catenin signaling is essential for transition from muscle stem cell proliferation to myogenic differentiation during regeneration (18), our findings suggest that the same developmental pathways that regulate muscle stem cell self-renewal also contribute to tumorigenesis in ERMS. In total, our work has identified the unconventional role of the canonical WNT/β-catenin pathway in regulating differentiation and self-renewal of ERMS.…”

mentioning

confidence: 84%

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Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma

Chen

DeRan

Ignatius

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

126

127

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Embryonal rhabdomyosarcoma (ERMS) is a common pediatric malignancy of muscle, with relapse being the major clinical challenge. Selfrenewing tumor-propagating cells (TPCs) drive cancer relapse and are confined to a molecularly definable subset of ERMS cells. To identify drugs that suppress ERMS self-renewal and induce differentiation of TPCs, a large-scale chemical screen was completed. Glycogen synthase kinase 3 (GSK3) inhibitors were identified as potent suppressors of ERMS growth through inhibiting proliferation and inducing terminal differentiation of TPCs into myosin-expressing cells. In support of GSK3 inhibitors functioning through activation of the canonical WNT/ β-catenin pathway, recombinant WNT3A and stabilized β-catenin also enhanced terminal differentiation of human ERMS cells. Treatment of ERMS-bearing zebrafish with GSK3 inhibitors activated the WNT/ β-catenin pathway, resulting in suppressed ERMS growth, depleted TPCs, and diminished self-renewal capacity in vivo. Activation of the canonical WNT/β-catenin pathway also significantly reduced selfrenewal of human ERMS, indicating a conserved function for this pathway in modulating ERMS self-renewal. In total, we have identified an unconventional tumor suppressive role for the canonical WNT/ β-catenin pathway in regulating self-renewal of ERMS and revealed therapeutic strategies to target differentiation of TPCs in ERMS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 84%

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Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma

Chen

DeRan

Ignatius

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

126

127

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“…In some normal adult tissues, Wnt / β -catenin signalling activity has been shown to mainly reside in stem or progenitor cells and to increase upon injury 17,18,49 . Interestingly, stem or progenitor cells are suggested to be fusion partners of transplanted bone marrowderived cells in tissue regeneration, at least in the intestine 3 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

et al. 2011

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Cell fusion has a critical role in various developmental processes, immune response, tissue homeostasis and regeneration, and possibly, in cancer. However, the signals that regulate cell fusion remain poorly understood. In a screen for novel targets of Wnt / β -catenin signalling, we identifi ed glial cells missing 1 ( GCM1 ), which encodes a transcription factor that is involved in epigenetic regulation and is critical for the fusion of syncytiotrophoblast (ST) cells. Here we show that β -catenin / BCL9-Like (BCL9L) / T-cell factor 4 (TCF4) signalling directly targets the GCM1 / syncytin pathway and thereby regulates the fusion of human choriocarcinoma cells. Furthermore, we show that the GCM1 / syncytin-B pathway is signifi cantly downregulated in the placenta of BCL9L-defi cient mice and that the fusion and differentiation of ST-II cells are blocked. Our results demonstrate a signal transduction pathway that regulates cell fusion, and may provide intriguing perspectives into the various biological and pathological processes that involve cell fusion.

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“…They are known to function at distinct phases of regeneration: with Notch functioning at the early phase to promote satellite cell activation and proliferation and Wnt at the later phase to promote myoblast differentiation [24][25][26]. In addition to Notch and Wnt, members of the interleukin-6 (IL-6) family of cytokines are also implicated in muscle differentiation and regeneration.…”

Section: Introductionmentioning

confidence: 99%

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

Xiao

Wang

et al. 2010

Cell Res

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Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.

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A Temporal Switch from Notch to Wnt Signaling in Muscle Stem Cells Is Necessary for Normal Adult Myogenesis

Cited by 561 publications

References 36 publications

Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma

Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma

Identification of a link between Wnt/β-catenin signalling and the cell fusion pathway

Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration

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