|
Article |
Address correspondence to P.S. Zammit, Muscle Cell Biology Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd., London W12 0NN, UK. Fax: 44 208 383 8264. email: peter.zammit{at}csc.mrc.ac.uk; or T.A. Partridge, email: terence.partridge{at}csc.mrc.ac.uk
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: stem; skeletal muscle regeneration; Pax7; MyoD; myogenin
V. Hudon's present address is McGill Cancer Center, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
Abbreviations used in this paper: EDL, extensor digitorum longus; MLC, myosin light chain; MRF, myogenic regulatory factor.
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The activation of satellite cells from a state of quiescence and their subsequent progression along the myogenic lineage are controlled by various transcription factors, chief among which are the myogenic regulatory factors (MRFs) Myf5, MyoD, myogenin, and MRF4 (for review see Zammit and Beauchamp, 2001). Myf5 and MyoD determine the myogenic lineage (Rudnicki et al., 1993; Tajbakhsh et al., 1996), whereas myogenin is essential for muscle cell differentiation (Hasty et al., 1993). In adult muscle, the Myf5 locus is active in quiescent satellite cells, with MyoD appearing during activation and myogenin following as differentiation begins (Fuchtbauer and Westphal, 1992; Grounds et al., 1992; Yablonka-Reuveni and Rivera, 1994; Cooper et al., 1999; Beauchamp et al., 2000). The absence of MyoD adversely affects muscle regeneration (Megeney et al., 1996), delaying the transition of satellite cellderived myoblasts from proliferation to differentiation (Sabourin et al., 1999; Yablonka-Reuveni et al., 1999). The role of Myf5 and myogenin during muscle regeneration has not been fully explored due to the perinatal mortality of the relevant null mice (Braun et al., 1992; Tajbakhsh et al., 1996). The expression of these MRFs in satellite cells provides a series of molecular landmarks for the transition from quiescence to activation and subsequent differentiation (Yablonka-Reuveni and Rivera, 1994; Beauchamp et al., 2000). Pax3 and Pax7, members of the paired box transcription factor family, have also been shown to be integral to muscle biology. Pax3 is essential for the migration of muscle precursors from the somites during development (Tajbakhsh et al., 1996) and is expressed in a small population of satellite cells (Buckingham et al., 2003), whereas Pax7 is required for satellite cell specification (Seale et al., 2000). However, the role of Pax7 during satellite cell activation and muscle regeneration has not yet been fully investigated.
An important question is: how is the satellite cell compartment maintained? For effective restoration of structure and function in the face of repeated injury (Sadeh et al., 1985; Luz et al., 2002), the pool of quiescent satellite cells must be replenished. There is evidence to support three scenarios that might achieve this. First, it has been suggested that satellite cells are a heterogeneous population, with some differentiating rapidly, whereas others are responsible for maintaining the pool (Rantanen et al., 1995). Second, there is a view that satellite cells are intrinsically homogenous and simultaneously activate but then adopt different fates to provide both new myonuclei and maintain the satellite cell pool (Moss and Leblond, 1971). More recently, it has been proposed that satellite cells may be part of a hierarchical system and represent a committed myogenic precursor that is restricted to providing myonuclei with satellite cell replacement occurring from a stem cell located within the muscle interstitium (Gussoni et al., 1999; Asakura et al., 2002) and/or outside muscle tissue (Fukada et al., 2002; LaBarge and Blau, 2002).
To explore the relative contribution of these three mechanisms to the maintenance of the satellite cell pool, we have used cultured myofibers, isolated complete with their retinue of satellite cells. When these myofibers are maintained in suspension culture, the associated satellite cells become activated, proliferate, and differentiate, while still exposed to signals from the myofiber (Beauchamp et al., 2000). This permits us to follow the fate of an entire cohort of satellite cells without any bias of selection. More importantly in the present context, the myofiber is isolated from potential exogenous sources of myogenic cells such as connective tissue and blood supply (Ferrari et al., 1998; LaBarge and Blau, 2002; Tamaki et al., 2002).
Here, we show that satellite cells can adopt divergent fates. Quiescent satellite cells become synchronously activated to coexpress both Pax7 and MyoD. Most satellite cells then undergo limited proliferation before down-regulating Pax7 and differentiating. Alternatively, satellite cell progeny can maintain Pax7 but lose MyoD. These Pax7+ve/MyoDve cells are typically located in clusters together with Pax7ve cells destined for differentiation. Pax7+ve/MyoDve cells persist and eventually divide slowly or not at all. Significantly, although most cells within a cluster express myogenin and differentiate, some retain the ability to be reactivated and reenter the cell cycle. Thus, our observations show that dividing satellite cells can either enter terminal differentiation or regain characteristics of quiescence. This finding suggests that the satellite cell pool is maintained via self-renewal, involving withdrawal from the terminal myogenic program, and may not require a contribution from elsewhere.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Satellite cells can adopt divergent fates
However, beyond 48 h, satellite cells exhibited a variety of Pax7, MyoD, and myogenin expression profiles (Table I). Immunostaining of the satellite cells present on wild-type myofibers after 72 h in culture (Fig. 1) showed that the majority contained MyoD (76.8%) and were divided into those that also coexpressed Pax7 (17.3%) and those that did not (59.5%; Fig. 1). At this time, a significant proportion of satellite cell progeny (23.2%; Table I) expressed Pax7 without MyoD (Fig. 1). The Pax7+ve/MyoDve cells were typically located in clusters (defined as four or more intimately associated cells; Fig. 1, e and f). Myofiber-associated satellite cells were also coimmunostained for MyoD and myogenin after 72 h in culture (Fig. 2) to determine how many cells were in the earliest phase of differentiation (Andres and Walsh, 1996). Of the myofiber-associated satellite cells that were immunostained, only 6% were myogenin+ve/MyoDve and 21.4% MyoD+ve/myogeninve, whereas the remaining 72.7% contained both MyoD and myogenin protein (Table I). Together, these observations show that virtually all satellite cells initially coexpress Pax7 and MyoD before proliferating and that most then commit to differentiation. Importantly though, at the same time some satellite cells begin to adopt a different fate, maintaining Pax7 but not MyoD. Furthermore, these Pax7+ve/MyoDve cells were still found when the growth medium was replaced each day, arguing that these cells had not simply withdrawn from myogenesis in response to mitogen depletion (unpublished data).
|
|
|
|
Satellite cells can down-regulate MyoD without committing to differentiation
Where do the Pax7+ve/MyoDve cells come from? As mentioned above, based on the pooled data from wild-type mice, one possible explanation could be the rapid expansion of a Pax7+ve/MyoDve population. However, the distribution of Pax7+ve/MyoDve cells at 24 h excludes this possibility. At 24 h, only 15% of myofibers contained Pax7+ve/MyoDve satellite cells, whereas by 72 h, virtually every myofiber (97%) did. Therefore, analysis of the myofiber distribution in the 3F-nlacZ-E study unequivocally shows that most of the Pax7+ve/MyoDve cells must have arisen from satellite cells that were initially Pax7+ve/MyoD+ve.
When is MyoD lost? Satellite cells on T0 myofibers are typically located as single cells distributed along the length of the entire myofiber; only 4 pairs were found among 59 satellite cells on 16 myofibers from mouse 3 and 5 pairs among 106 satellite cells on 19 myofibers from mouse 4. Therefore, the pairs and small groups of satellite cells observed at 48 h are probably clonal in origin. Rare instances of clones of satellite cells could be observed that contained both Pax7+ve/MyoD+ve and Pax7+ve/MyoDve cells. An example is shown in Fig. 3, where the cell surface protein CD34 (Beauchamp et al., 2000) marks four satellite cells, only three of which coexpress MyoD (Fig. 3, a and b). In addition, MyoDve cells could incorporate BrdU, showing that they were the progeny of an activated satellite cell, and not rare quiescent MyoDve cells that had failed to activate (Fig. 3, ce). To assess the frequency of this event, myofibers were cultured in the presence of BrdU for 48 h and then immunostained. Of 50 pairs of touching BrdU+ve cells, presumed to have recently divided, 43 pairs were symmetrically MyoD+ve, whereas 7 pairs (14%) had conspicuously higher levels of MyoD in one daughter than the other. If we recalculate, taking single and groups of satellite cells into account, the 14% that down-regulate MyoD in the touching satellite cell pairs becomes 2.2% of the total satellite cells present.
|
Some Pax7+ve/ MyoDve cells eventually divide slowly or stop cycling
Until 72 h, the majority of satellite cells were cycling rapidly, as shown by the presence of PCNA in their nuclei (Fig. 4, ac). However, from 72 h onwards the number of PCNA+ve cells dropped markedly, as differentiation ensued. The low level of BrdU incorporation after a 24-h pulse from 96120 h confirmed that very few satellite cells were still cycling. Interestingly, 42.5% of the Pax7+ve cells (
20 myofibers from each of three mice) also failed to incorporate BrdU during this time, indicating that they were either cycling slowly (i.e., not entering S phase during the 24-h period of the pulse) or were quiescent (Fig. 4, df). Crucially, Pax7+ve cells were almost all negative for MyoD at 120 h (Fig. 4, gi), showing that the Pax7+ve/MyoDve phenotype was not transient but persisted until at least 120 h, the latest time point examined in this study. In addition, virtually no expression of MyoD (Fig. 4, gi) or myogenin (not depicted) was detectable in any satellite cells at this time, demonstrating that the expression of these two MRFs is transient. Thus, some satellite cells cultured in association with their myofiber maintain expression of Pax7, down-regulate MyoD, and begin to cycle slowly or not at all; all characteristics of quiescent satellite cells.
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
On the basis of our observations on the alternate fates adopted by satellite cells, we propose a model for satellite cell self-renewal (Fig. 6). Virtually all quiescent satellite cells coexpress Pax7 and MyoD within a few hours of activation. After this point, phenotypic and behavioral diversification becomes apparent. Most cells undergo rapid but limited proliferation and down-regulate Pax7 as they begin to differentiate, consistent with previous descriptions of MyoD and myogenin expression during satellite cell activation (Grounds et al., 1992; Yablonka-Reuveni and Rivera, 1994; Cooper et al., 1999). This behavior shows close parallels to the transit-amplifying population resident in skin (Watt, 2002). However, not all Pax7+ve/MyoD+ve satellite cell progeny follow this highly coordinated program of gene expression toward a differentiated state. Others adopt an alternative fate in which Pax7 is maintained but MyoD is lost as the cells withdraw from differentiation. Later, Pax7+ve/MyoDve cells are observed in clusters, together with Pax7ve cells that are destined to differentiate to replace lost myonuclei. The Pax7+ve/MyoDve cells then become quiescent, thus maintaining the satellite cell pool. This model is consistent with observations of satellite cells during regeneration in vivo where most rapidly differentiate after only a limited number of divisions, whereas a minority proliferate for an extended period (Grounds and McGeachie, 1987; McGeachie and Grounds, 1987; Rantanen et al., 1995).
|
What dictates the divergent fates of satellite cells? Is it an innate, lineage based, heterogeneity of the satellite cell population, or differences within the microenvironment on the myofiber and/or within the cell cluster? The satellite cell pool is heterogeneous by several criteria. For example, although the majority of quiescent satellite cells in limb muscle transcribe Myf5 and contain M-cadherin and CD34 protein, a minority are negative for any of these markers (Beauchamp et al., 2000). On a larger scale, the majority of muscles in the Pax3nLacZ/+mouse contain only rare Pax3+ve satellite cells, but some show more widespread expression (Buckingham et al., 2003). Functional heterogeneity within muscle is also evident, with at least two populations identified by their differential sensitivity to irradiation (Heslop et al., 2000). Clonal studies also suggest heterogeneity as defined by both proliferation rate and clonogenic capacity (Schultz and Lipton, 1982; Molnar et al., 1996). Furthermore, during both growth and regeneration, satellite cells can clearly be divided with respect to their growth factor requirements for proliferation (Yablonka-Reuveni and Rivera, 1994), by their rate of cell division (Grounds and McGeachie, 1987; McGeachie and Grounds, 1987; Rantanen et al., 1995; Schultz, 1996), and by the myosin heavy chain isoforms they express upon differentiation (Hoh et al., 1988; Hoh and Hughes, 1991; Rosenblatt et al., 1996).
That divergence in fate of the Pax7+ve/MyoD+ve satellite cells occurs without the synchronizing signal of mitogen reduction indicates that this is a normal part of the program of satellite cell replacement. However, it remains to be shown whether satellite cell heterogeneity reflects the stochaistic generation of diversity within a dynamic system or a distinct lineage-based subpopulation. We have shown that this divergence in fate of satellite cells occurs reproducibly in cultures on suspended myofibers. This finding contrasts with the behavior of satellite cells that are allowed to migrate from a myofiber onto the tissue culture substrate, where Pax7+ve/MyoDve cells are rarely observed and three-dimensional clusters do not form (unpublished data). This suggests that the culture of satellite cells on isolated myofibers in suspension is an apposite model to mimic the self-regulatory events of myogenesis during muscle regeneration in vivo. The potential importance of environmental regulation is also suggested by the behavior of primary myoblasts or myogenic cell lines induced to differentiate by mitogen withdrawal. Although most differentiate, a population of "reserve cells" has been described that stop dividing yet retain the ability to reenter cell cycle and differentiate when passaged (Kitzmann et al., 1998; Yoshida et al., 1998). Significantly, reserve cells can be generated from clones, supporting the notion that this is not an intrinsic property of a permanent subset but that any myoblast can acquire this behavioral phenotype (Baroffio et al., 1996).
Therefore, we suggest that generation of Pax7+ve/MyoDve cells is not a cell autonomous event, but instead arises from signaling between the myofiber and satellite cell, or the microenvironment within cell clusters, as indicated in our model (Fig. 6). Maintenance in vitro of satellite cells in their native position under the basal lamina and adjacent to the myofiber preserves such contact-dependent interactions and signaling. It may be that an instructive signal from the myofiber plays some part in directing the cell to become quiescent, much as IL-4 secreted by myotubes controls the recruitment of further myoblasts (Horsley et al., 2003). It is also possible that the differentiation of some satellite cells may signal others to become quiescent, possibly using systems used to direct cell fate elsewhere, such as the Notch signaling pathway (Artavanis-Tsakonas et al., 1999), components of which are expressed by satellite cells (Conboy and Rando, 2002).
The single fiber culture model used here also has the advantage that the source of cells is defined as satellite cells, i.e., those resident under the basal lamina, thus isolating the process of satellite cell activation and renewal from potential contributions from elsewhere. This finding is important in light of several recent studies that have shown that other cells isolated from muscle and from a diverse range of tissues are able to adopt a myogenic phenotype, albeit at a very low frequency (Ferrari et al., 1998; Gussoni et al., 1999; LaBarge and Blau, 2002).
Side population stem cells, characterized by their ability to exclude Hoescht dye, can be isolated from muscle tissue and have been shown to be distinct from satellite cells (Gussoni et al., 1999; Jackson et al., 1999; Asakura et al., 2002). Side population cells can contribute to both the hematopoietic and myogenic lineages (Gussoni et al., 1999; Asakura et al., 2002), leading to the suggestion that they are a normal, routine source of satellite cells. Myogenic precursors also reside in the interstitium of muscle (Tamaki et al., 2002), and blood vesselderived mesoangioblasts too have myogenic potential (De Angelis et al., 1999; Cusella De Angelis et al., 2003; Sampaolesi et al., 2003). Moreover, transplantation studies show that cells derived from various nonmuscle tissues can contribute to muscle (for review see Grounds et al., 2002). The most intriguing of these nonmuscle sources is bone marrow, which produces cells that are able to move into the satellite cell niche, arriving via the circulation following bone marrow grafts (Fukada et al., 2002; LaBarge and Blau, 2002), suggesting that this could also be a usual source of myogenic cells. However, the number of myofibers with a donor contribution is very low and does not increase significantly with time in either mouse (Ferrari et al., 2001; Brazelton et al., 2003) or man (Gussoni et al., 2002), implying that either bone marrow cells are unable to contribute to any great extent to the stem cell compartment within muscle or to be continually recruited.
The results presented here, showing that satellite cells can adopt divergent fates, suggest that the satellite cell pool is maintained by self-renewal and that this is independent of a contribution from outside. Although this finding does not exclude participation by other cells to myogenesis in vivo, possibly to augment the number of myoblasts during severe muscle regeneration, no evidence has been produced of more than a minor contribution from these other sources. Indeed, the ablation of the satellite cell pool by irradiation suggests that cells from outside of muscle are not able to restore functional regeneration (Heslop et al., 2000). Certainly, no such contribution appears to be required because satellite cells associated with a muscle fiber are capable of producing enough myoblasts to entirely replace that myofiber in a time scale consistent with in vivo regeneration (Zammit et al., 2002).
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Tissue preparation and single fiber isolation
Mice were killed by cervical dislocation before the EDL muscles were carefully removed. Myofibers were isolated as described previously (Rosenblatt et al., 1995) and either fixed for 520 min in 4% PFA/PBS or cultured.
Myofiber culture
For suspension culture, myofibers were incubated in growth medium (DME with 10% [vol/vol] horse serum [PAA Laboratories] and 0.5% [vol/vol] chick embryo extract [ICN Biomedicals]) at 37°C in 5% CO2. For adherent cultures, isolated clusters were placed in 24-well Primaria plates (Marathon) coated with 1 mg/ml of Matrigel (Collaborative Research Inc.). Growth medium was added and the cultures maintained at 37°C in 5% CO2. Where used, BrdU was added to the medium at a final concentration of 10 µM. Myofibers and cells were fixed in 4% PFA/PBS for 520 min.
Immunostaining
Fixed myofibers were permeabilized with 0.5% (vol/vol) Triton X-100/PBS and blocked using 20% (vol/vol) goat serum/PBS, as described previously (Beauchamp et al., 2000). Primary antibodies used were monoclonal rat anti-BrdU (clone BU1/75; Abcam), monoclonal mouse antimyogenin (clone F5D; DakoCytomation or Developmental Studies Hybridoma Bank [DSHB]), anti-MyoD1 (clone 5.8a; DakoCytomation), anti-Pax7 (DSHB), anti-PCNA (clone PC10; DakoCytomation), rabbit polyclonal anti-MyoD (Santa Cruz Biotechnology, Inc.), antimyogenin (Santa Cruz Biotechnology, Inc.), antiphosphorylated Histone H1 (Upstate Biotechnology), and antiphosphorylated Histone H3 (Upstate Biotechnology). Primary antibodies were visualized with fluorochrome-conjugated secondary antibodies (Molecular Probes) before mounting in Faramount fluorescent mounting medium (DakoCytomation) containing 100 ng/ml DAPI.
Histology
To visualize ß-galactosidase activity, immunostained myofibers were incubated in X-gal solution (4 mM potassium ferrocyanide, 4 mM potassium ferricyanide, 2 mM MgCl2, 400 µg/ml X-gal, and 0.02% NP-40 in PBS) for 15 min at RT. Myofibers were rinsed several times in PBS and mounted in Faramount aqueous mounting medium containing 100 ng/ml DAPI.
Quantification
For wild-type mice, the number of cells in each category (i.e., Pax7+ve/MyoDve, Pax7+ve/MyoD+ve, or Pax7ve/MyoD+ve) were counted and expressed as a percentage of the total immunostained cells on the myofiber, and the data from multiple myofibers were pooled to give a population mean (± SEM). For 3F-nlacZ-E mice, the absolute number of satellite cells per myofiber was determined using unquenched DAPI fluorescence after X-gal incubation. Each cell was categorized by immunostaining, and the data from multiple myofibers were pooled to give a population mean (± SEM) for cells in each category and also expressed as a percentage of the total satellite cell pool.
Image capture
Immunostained myofibers were viewed on an epifluorescence microscope (model Axiophot; Carl Zeiss MicroImaging, Inc.) using a 40x/0.75 Ph2-Neofluar lens. Digital images were acquired with a Charge-Coupled Device (model RTE/CCD-1300-Y; Princeton Instruments Inc.) at 10°C using Metamorph software version 4.5r5 (Universal Imaging Corp). Live cells were viewed on a microscope (model Axiovert 100; Carl Zeiss MicroImaging, Inc.) with Achrostigmat lenses (Carl Zeiss MicroImaging, Inc.) and digital images acquired on a three-color Charge-Coupled Device (model DXC-930P; Sony) using Sirius VI software version 2.0c (Optivision). Images were optimized globally for contrast and brightness and assembled into figures using Adobe Photoshop 6.0.1.
![]() |
Acknowledgments |
---|
This work was supported by the Medical Research Council, European Community (EC) Biotechnology grant BIO4 CT 95-0228, EC Framework 5 QLRT-99-00020, EC Framework 5QLK6-1999-02034, and the British Council/EGIDE Alliance 2000/2001 grant PN 00.172. P.S. Zammit was funded by the Muscular Dystrophy Association and the Medical Research Council. Y. Nagata was funded by the Japan Scholarship Foundation. J.P. Golding was funded by EC Framework 5QLK6-1999-02034 and a Medical Research Council Collaborative Career Development Fellowship in Stem Cell Research. T. Partridge was partially funded by a Winter Fuel Payment from the UK Department for Work and Pensions. The Muscle Cell Biology Group also received support from EC Biotechnology grants BIO4 CT95-0284 and BMH4 CT97-2767 and the Leopold Muller Foundation.
Note added in proof. Recent work by Yablonka-Reuveni and associates (Halevy, O., Y. Piestun, M. Allouh, B. Rosser, Y. Rinkevich, R. Reshef, I. Rozenboim, M. Wleklinski-Lee, and Z. Yablonka-Reuveni. 2004. Dev. Dynam. In Press) is in accordance with our model of satellite cell self-renewal. These authors show that Pax7+ve/MyoDve cells can be observed in cultures initiated from wing chicken muscle and that a single cell can give rise to both Pax7+ve/MyoDve and Pax7+ve/MyoD+ve progeny.
Submitted: 2 December 2003
Accepted: 14 June 2004
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Andres, V., and K. Walsh. 1996. Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis. J. Cell Biol. 132:657666.[Abstract]
Artavanis-Tsakonas, S., M.D. Rand, and R.J. Lake. 1999. Notch signaling: cell fate control and signal integration in development. Science. 284:770776.
Asakura, A., P. Seale, A. Girgis-Gabardo, and M.A. Rudnicki. 2002. Myogenic specification of side population cells in skeletal muscle. J. Cell Biol. 159:123134.
Baroffio, A., M. Hamann, L. Bernheim, M.L. Bochaton-Piallat, G. Gabbiani, and C.R. Bader. 1996. Identification of self-renewing myoblasts in the progeny of single human muscle satellite cells. Differentiation. 60:4757.[CrossRef][Medline]
Beauchamp, J.R., L. Heslop, D.S. Yu, S. Tajbakhsh, R.G. Kelly, A. Wernig, M.E. Buckingham, T.A. Partridge, and P.S. Zammit. 2000. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J. Cell Biol. 151:12211234.
Bischoff, R. 1986. Proliferation of muscle satellite cells on intact myofibers in culture. Dev. Biol. 115:129139.[Medline]
Blaveri, K., L. Heslop, D.S. Yu, J.D. Rosenblatt, J.G. Gross, T.A. Partridge, and J.E. Morgan. 1999. Patterns of repair of dystrophic mouse muscle: studies on isolated fibers. Dev. Dyn. 216:244256.[CrossRef][Medline]
Braun, T., M.A. Rudnicki, H.H. Arnold, and R. Jaenisch. 1992. Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell. 71:369382.[Medline]
Brazelton, T.R., M. Nystrom, and H.M. Blau. 2003. Significant differences among skeletal muscles in the incorporation of bone marrow-derived cells. Dev. Biol. 262:6474.[CrossRef][Medline]
Buckingham, M., L. Bajard, T. Chang, P. Daubas, J. Hadchouel, S. Meilhac, D. Montarras, D. Rocancourt, and F. Relaix. 2003. The formation of skeletal muscle: from somite to limb. J. Anat. 202:5968.[CrossRef][Medline]
Conboy, I.M., and T.A. Rando. 2002. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev. Cell. 3:397409.[Medline]
Cooper, R.N., S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham, and G.S. Butler-Browne. 1999. In vivo satellite cell activation via Myf5 and MyoD in regenerating mouse skeletal muscle. J. Cell Sci. 112:28952901.
Cusella De Angelis, M.G., G. Balconi, S. Bernasconi, L. Zanetta, R. Boratto, D. Galli, E. Dejana, and G. Cossu. 2003. Skeletal myogenic progenitors in the endothelium of lung and yolk sac. Exp. Cell Res. 290:207216.[CrossRef][Medline]
De Angelis, L., L. Berghella, M. Coletta, L. Lattanzi, M. Zanchi, M.G. Cusella-De Angelis, C. Ponzetto, and G. Cossu. 1999. Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. J. Cell Biol. 147:869878.
Ferrari, G., G. Cusella-De Angelis, M. Coletta, E. Paolucci, A. Stornaiuolo, G. Cossu, and F. Mavilio. 1998. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 279:15281530.
Ferrari, G., A. Stornaiuolo, and F. Mavilio. 2001. Failure to correct murine muscular dystrophy. Nature. 411:10141015.[CrossRef][Medline]
Fuchtbauer, E.M., and H. Westphal. 1992. MyoD and myogenin are coexpressed in regenerating skeletal muscle of the mouse. Dev. Dyn. 193:3439.[Medline]
Fukada, S., Y. Miyagoe-Suzuki, H. Tsukihara, K. Yuasa, S. Higuchi, S. Ono, K. Tsujikawa, S. Takeda, and H. Yamamoto. 2002. Muscle regeneration by reconstitution with bone marrow or fetal liver cells from green fluorescent protein-gene transgenic mice. J. Cell Sci. 115:12851293.
Grounds, M.D., and J.K. McGeachie. 1987. A model of myogenesis in vivo, derived from detailed autoradiographic studies of regenerating skeletal muscle, challenges the concept of quantal mitosis. Cell Tissue Res. 250:563569.[Medline]
Grounds, M.D., K.L. Garrett, M.C. Lai, W.E. Wright, and M.W. Beilharz. 1992. Identification of skeletal muscle precursor cells in vivo by use of MyoD1 and myogenin probes. Cell Tissue Res. 267:99104.[Medline]
Grounds, M.D., J.D. White, N. Rosenthal, and M.A. Bogoyevitch. 2002. The role of stem cells in skeletal and cardiac muscle repair. J. Histochem. Cytochem. 50:589610.
Gussoni, E., Y. Soneoka, C.D. Strickland, E.A. Buzney, M.K. Khan, A.F. Flint, L.M. Kunkel, and R.C. Mulligan. 1999. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 401:390394.[CrossRef][Medline]
Gussoni, E., R.R. Bennett, K.R. Muskiewicz, T. Meyerrose, J.A. Nolta, I. Gilgoff, J. Stein, Y.M. Chan, H.G. Lidov, C.G. Bonnemann, et al. 2002. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J. Clin. Invest. 110:807814.
Hasty, P., A. Bradley, J.H. Morris, D.G. Edmondson, J.M. Venuti, E.N. Olson, and W.H. Klein. 1993. Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature. 364:501506.[CrossRef][Medline]
Heslop, L., J.E. Morgan, and T.A. Partridge. 2000. Evidence for a myogenic stem cell that is exhausted in dystrophic muscle. J. Cell Sci. 113:22992308.
Heslop, L., J.R. Beauchamp, S. Tajbakhsh, M.E. Buckingham, T.A. Partridge, and P.S. Zammit. 2001. Transplanted primary neonatal myoblasts can give rise to functional satellite cells as identified using the Myf5nlacZ/+ mouse. Gene Ther. 8:778783.[CrossRef][Medline]
Hoh, J.F., and S. Hughes. 1991. Basal lamina and superfast myosin expression in regenerating cat jaw muscle. Muscle Nerve. 14:398406.[Medline]
Hoh, J.F., S. Hughes, and J.F. Hoy. 1988. Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds. J. Muscle Res. Cell Motil. 9:5972.[Medline]
Horsley, V., K.M. Jansen, S.T. Mills, and G.K. Pavlath. 2003. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell. 113:483494.[Medline]
Jackson, K.A., T. Mi, and M.A. Goodell. 1999. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl. Acad. Sci. USA. 96:1448214486.
Kelly, R., S. Alonso, S. Tajbakhsh, G. Cossu, and M. Buckingham. 1995. Myosin light chain 3F regulatory sequences confer regionalized cardiac and skeletal muscle expression in transgenic mice. J. Cell Biol. 129:383396.[Abstract]
Kitzmann, M., G. Carnac, M. Vandromme, M. Primig, N.J. Lamb, and A. Fernandez. 1998. The muscle regulatory factors MyoD and myf-5 undergo distinct cell cyclespecific expression in muscle cells. J. Cell Biol. 142:14471459.
Kondo, T., and M. Raff. 2000. Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. Science. 289:17541757.
LaBarge, M.A., and H.M. Blau. 2002. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell. 111:589601.[Medline]
Lindon, C., D. Montarras, and C. Pinset. 1998. Cell cycleregulated expression of the muscle determination factor Myf5 in proliferating myoblasts. J. Cell Biol. 140:111118.
Luz, M.A., M.J. Marques, and H. Santo Neto. 2002. Impaired regeneration of dystrophin-deficient muscle fibers is caused by exhaustion of myogenic cells. Braz. J. Med. Biol. Res. 35:691695.[Medline]
McGeachie, J.K., and M.D. Grounds. 1987. Initiation and duration of muscle precursor replication after mild and severe injury to skeletal muscle of mice. An autoradiographic study. Cell Tissue Res. 248:125130.[Medline]
Megeney, L.A., B. Kablar, K. Garrett, J.E. Anderson, and M.A. Rudnicki. 1996. MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes Dev. 10:11731183.[Abstract]
Molnar, G., M.L. Ho, and N.A. Schroedl. 1996. Evidence for multiple satellite cell populations and a non-myogenic cell type that is regulated differently in regenerating and growing skeletal muscle. Tissue Cell. 28:547556.[Medline]
Moss, F.P., and C.P. Leblond. 1971. Satellite cells as the source of nuclei in muscles of growing rats. Anat. Rec. 170:421435.[Medline]
Rantanen, J., T. Hurme, R. Lukka, J. Heino, and H. Kalimo. 1995. Satellite cell proliferation and the expression of myogenin and desmin in regenerating skeletal muscle: evidence for two different populations of satellite cells. Lab. Invest. 72:341347.[Medline]
Rosenblatt, J.D., A.I. Lunt, D.J. Parry, and T.A. Partridge. 1995. Culturing satellite cells from living single muscle fiber explants. In Vitro Cell. Dev. Biol. Anim. 31:773779.[Medline]
Rosenblatt, J.D., D.J. Parry, and T.A. Partridge. 1996. Phenotype of adult mouse muscle myoblasts reflects their fiber type of origin. Differentiation. 60:3945.[CrossRef][Medline]
Rudnicki, M.A., P.N. Schnegelsberg, R.H. Stead, T. Braun, H.H. Arnold, and R. Jaenisch. 1993. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell. 75:13511359.[Medline]
Sabourin, L.A., A. Girgis-Gabardo, P. Seale, A. Asakura, and M.A. Rudnicki. 1999. Reduced differentiation potential of primary MyoD/ myogenic cells derived from adult skeletal muscle. J. Cell Biol. 144:631643.
Sadeh, M., K. Czyewski, and L.Z. Stern. 1985. Chronic myopathy induced by repeated bupivacaine injections. J. Neurol. Sci. 67:229238.[CrossRef][Medline]
Sampaolesi, M., Y. Torrente, A. Innocenzi, R. Tonlorenzi, G. D'Antona, M.A. Pellegrino, R. Barresi, N. Bresolin, M.G. De Angelis, K.P. Campbell, et al. 2003. Cell therapy of -sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science. 301:487492.
Schmalbruch, H., and D.M. Lewis. 2000. Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles. Muscle Nerve. 23:617626.[CrossRef][Medline]
Schultz, E. 1996. Satellite cell proliferative compartments in growing skeletal muscles. Dev. Biol. 175:8494.[CrossRef][Medline]
Schultz, E., and B.H. Lipton. 1982. Skeletal muscle satellite cells: changes in proliferation potential as a function of age. Mech. Ageing Dev. 20:377383.[CrossRef][Medline]
Schultz, E., M.C. Gibson, and T. Champion. 1978. Satellite cells are mitotically quiescent in mature mouse muscle: an EM and radioautographic study. J. Exp. Zool. 206:451456.[Medline]
Seale, P., L.A. Sabourin, A. Girgis-Gabardo, A. Mansouri, P. Gruss, and M.A. Rudnicki. 2000. Pax7 is required for the specification of myogenic satellite cells. Cell. 102:777786.[Medline]
Snow, M.H. 1977. Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. II. An autoradiographic study. Anat. Rec. 188:201217.[Medline]
Snow, M.H. 1978. An autoradiographic study of satellite cell differentiation into regenerating myotubes following transplantation of muscles in young rats. Cell Tissue Res. 186:535540.[Medline]
Tajbakhsh, S., D. Rocancourt, and M. Buckingham. 1996. Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice. Nature. 384:266270.[CrossRef][Medline]
Tamaki, T., A. Akatsuka, K. Ando, Y. Nakamura, H. Matsuzawa, T. Hotta, R.R. Roy, and V.R. Edgerton. 2002. Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J. Cell Biol. 157:571577.
Watt, F.M. 2002. The stem cell compartment in human interfollicular epidermis. J. Dermatol. Sci. 28:173180.[CrossRef][Medline]
Weintraub, H., R. Davis, S. Tapscott, M. Thayer, M. Krause, R. Benezra, T.K. Blackwell, D. Turner, R. Rupp, S. Hollenberg, et al. 1991. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 251:761766.[Medline]
Whalen, R.G., J.B. Harris, G.S. Butler-Browne, and S. Sesodia. 1990. Expression of myosin isoforms during notexin-induced regeneration of rat soleus muscles. Dev. Biol. 141:2440.[Medline]
Yablonka-Reuveni, Z., and A.J. Rivera. 1994. Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers. Dev. Biol. 164:588603.[CrossRef][Medline]
Yablonka-Reuveni, Z., M.A. Rudnicki, A.J. Rivera, M. Primig, J.E. Anderson, and P. Natanson. 1999. The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. Dev. Biol. 210:440455.[CrossRef][Medline]
Yoshida, N., S. Yoshida, K. Koishi, K. Masuda, and Y. Nabeshima. 1998. Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates reserve cells. J. Cell Sci. 111:769779.
Zammit, P., and J. Beauchamp. 2001. The skeletal muscle satellite cell: stem cell or son of stem cell? Differentiation. 68:193204.[CrossRef][Medline]
Zammit, P.S., L. Heslop, V. Hudon, J.D. Rosenblatt, S. Tajbakhsh, M.E. Buckingham, J.R. Beauchamp, and T.A. Partridge. 2002. Kinetics of myoblast proliferation show that resident satellite cells are competent to fully regenerate skeletal muscle fibers. Exp. Cell Res. 281:3949.[CrossRef][Medline]
Related Article