MyoD is required for myogenic stem cell function in adult skeletal muscle.

Megeney, Lynn A.; Kablar, Boris; Garrett, Kerryn L.; Anderson, Judy E.; Rudnicki, Michael A.

doi:10.1101/gad.10.10.1173

Cited by 642 publications

(578 citation statements)

References 43 publications

(50 reference statements)

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“…The adult skeletal muscle in mice lacking MyoD (MyoD Ϫ/Ϫ ) displays a deficiency in regeneration and strongly supports the assertion that MyoD plays an essential role in regulating the satellite cell myogenic program (13). In addition, we and other groups have demonstrated that satellite cell-derived primary myoblasts isolated from adult MyoD Ϫ/Ϫ mice display an accelerated growth rate and delayed terminal differentiation (2,(14)(15)(16)(17)(18)(19).…”

mentioning

confidence: 63%

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

Asakura

Hirai

Kablar

et al. 2007

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

109

114

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MyoD is a myogenic master transcription factor that plays an essential role in muscle satellite cell (muscle stem cell) differentiation. To further investigate the function of MyoD in satellite cells, we examined the transplantation of satellite cell-derived myoblasts lacking the MyoD gene into regenerating skeletal muscle. After injection into injured muscle, MyoD ؊/؊ myoblasts engrafted with significantly higher efficiency compared with wild-type myoblasts. In addition, MyoD ؊/؊ myoblast-derived satellite cells were detected underneath the basal lamina of muscle fibers, indicating the self-renewal property of MyoD ؊/؊ myoblasts. To gain insights into MyoD gene deficiency in muscle stem cells, we investigated the pathways regulated by MyoD by GeneChip microarray analysis of gene expression in wild-type and MyoD ؊/؊ myoblasts. MyoD deficiency led to down-regulation of many muscle-specific genes and up-regulation of some stem cell markers. Importantly, in MyoD ؊/؊ myoblasts, many antiapoptotic genes were up-regulated, whereas genes known to execute apoptosis were downregulated. Consistent with these gene expression profiles, MyoD ؊/؊ myoblasts were revealed to possess remarkable resistance to apoptosis and increased survival compared with wild-type myoblasts. Forced expression of MyoD or the proapoptotic protein Puma increased cell death in MyoD ؊/؊ myoblasts. Therefore, MyoD ؊/؊ myoblasts may preserve stem cell characteristics, including their resistance to apoptosis, expression of stem cell markers, and efficient engraftment and contribution to satellite cells after transplantation. Furthermore, our data offer evidence for improved therapeutic stem cell transplantation for muscular dystrophy, in which suppression of MyoD in myogenic progenitors would be beneficial to therapy by providing a selective advantage for the expansion of stem cells.apoptosis ͉ cell therapy ͉ microarrays ͉ muscular dystrophy ͉ satellite cell

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mentioning

confidence: 63%

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

Asakura

Hirai

Kablar

et al. 2007

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

109

114

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“…According to an essential role of Pax7 in regeneration, Pax 7 is necessary for the expression of MyoD (Seale et al, 2004). And MyoD appears to have a unique role in promoting satellitemediated regeneration (Megeney et al, 1996). Recently, Polesskaya et al, observed that upon muscle injury there is an up-regulation of several Wnt isoforms (Wnt 5a, 5b, 7a, and 7b) suggesting a role for these proteins in muscle regeneration (Polesskaya et al, 2003).…”

Section: Developmental and Adult Myogenesis: Common Mechanisms And Mementioning

confidence: 99%

The epigenetic network regulating muscle development and regeneration

Palacios

Puri

2005

Journal Cellular Physiology

105

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This review focuses on our current knowledge of the epigenetic changes regulating gene expression at the chromatin and DNA level, independently on the primary DNA sequence, to reprogram the nuclei of muscle precursors during developmental myogenesis and muscle regeneration. These epigenetic marks provide the blueprint by which the extra-cellular cues are interpreted at the nuclear level by the transcription machinery to select the repertoire of tissue-specific genes to be expressed. The reversibility of some of these changes necessarily reflects the dynamic nature of skeletal myogenesis, which entails the progression through two antagonistic processes-proliferation and differentiation. Other epigenetic modifications are instead associated to events conventionally considered as irreversible-e.g. maintenance of lineage commitment and terminal differentiation. However, recent results support the possibility that these events can be reversed, at least upon certain experimental conditions, thereby revealing a dynamic nature of many of the epigenetic modifications underlying skeletal myogenesis. The elucidation of the epigenetic network that regulates transcription during developmental myogenesis and muscle regeneration might provide the information instrumental to devise pharmacological interventions toward selective manipulation of gene expression to promote regeneration of skeletal muscles and possibly other tissue.

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“…To test their muscle differentiation potential in vitro, we cultured hMSC-PAX3 and hMSC-Vector cells under several muscle inductive conditions (#2, 10% FBS, bFGF, neuregulin, PDGF-AA and forskolin) [29]; #3, 2% HS [40], and #4, 10% FBS and 5-azacitidine for up to 4 weeks [26] (Fig. 4), along with control conditions, including basic MSC medium (#1, 16.5% FBS) [39], complete expansion medium (#5, 10% FBS and PDGF-BB/EGF) [39], and expansion medium without growth factors (#6).…”

Section: Pax3 Promotes the Activation Of The Myogenic Program In Primmentioning

confidence: 99%

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Gang

Darabi

Bosnakovski

et al. 2009

Experimental Cell Research

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Mesenchymal stem cell preparations have been proposed for muscle regeneration in musculoskeletal disorders. Although MSCs have great in vitro expansion potential and possess the ability to differentiate into several mesenchymal lineages, myogenesis has proven to be much more difficult to induce. We have recently demonstrated that Pax3, the master regulator of the embryonic myogenic program, enables the in vitro differentiation of a murine mesenchymal stem cell line (MSCB9-Pax3) into myogenic progenitors. Here we show that injection of these cells into cardiotoxin-injured muscles of immunodeficient mice leads to the development of muscle tumors, resembling rhabdomyosarcomas. We then extended these studies to primary human mesenchymal stem cells (hMSCs) isolated from bone marrow. Upon genetic modification with a lentiviral vector encoding PAX3, hMSCs activated the myogenic program as demonstrated by expression of myogenic regulatory factors. Upon transplantation, the PAX3-modified MSCs did not generate rhabdomyosarcomas but rather, resulted in donor-derived myofibers. These were found at higher frequency in PAX3-transduced hMSCs than in mock-transduced MSCs. Nonetheless, neither engraftment of PAX3-modified or unmodified MSCs resulted in improved contractility.Thus these findings suggest that limitations remain to be overcome before MSC preparations result in effective treatment for muscular dystrophies.

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MyoD is required for myogenic stem cell function in adult skeletal muscle.

Cited by 642 publications

References 43 publications

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

The epigenetic network regulating muscle development and regeneration

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

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