A Unique Twist-Dependent Progenitor Cell Contributes to Adult Skeletal Muscle [Tw2 vs Pax7 fresh sort]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84379 | GEO | 2017/01/13
SECONDARY ACCESSION(S): PRJNA329011
REPOSITORIES: GEO
Similar Datasets
Project description:Skeletal muscle possesses remarkable regenerative potential due to satellite cells, a stem cell population located beneath the muscle basal lamina. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a unique myogenic lineage that resides outside the basal lamina of adult muscle and contributes specifically to type IIb/x myofibers during adulthood and muscle regeneration. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro and can fuse with satellite cells. Transplantation of Tw2+ progenitors into adult mice is sufficient to reconstitute new myofibers, and genetic ablation of endogenous Tw2+ progenitors causes wasting of type IIb myofibers. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that suppress Tw2 expression. Tw2-expressing progenitors represent a previously unrecognized, fiber-type specific progenitor cell involved in muscle growth and regeneration.
2017-01-13 | GSE84378 | GEO
Project description:Skeletal muscle possesses remarkable regenerative potential due to satellite cells, a stem cell population located beneath the muscle basal lamina. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a unique myogenic lineage that resides outside the basal lamina of adult muscle and contributes specifically to type IIb/x myofibers during adulthood and muscle regeneration. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro and can fuse with satellite cells. Transplantation of Tw2+ progenitors into adult mice is sufficient to reconstitute new myofibers, and genetic ablation of endogenous Tw2+ progenitors causes wasting of type IIb myofibers. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that suppress Tw2 expression. Tw2-expressing progenitors represent a previously unrecognized, fiber-type specific progenitor cell involved in muscle growth and regeneration.
2017-01-13 | GSE84377 | GEO
Project description:Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite deregulate the expression of basal lamina components and adhesion molecules like integrin a7, collagen XVIIIa1, Megf10 and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers. Gene expression analysis using total RNA from FACS-isolated Vcam-1+/CD31-/CD45-/Sca1- embryonic muscle progenitor cells from E17.5 back muscle tissue of MyoD-/-, Pax3cre/+;Rbpjflox/flox;MyoD-/- and Pax3cre/+;DnMamlflox/flox;MyoD-/- mice.
2012-12-31 | E-GEOD-39379 | biostudies-arrayexpress
Project description:Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite deregulate the expression of basal lamina components and adhesion molecules like integrin a7, collagen XVIIIa1, Megf10 and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers.
2012-12-31 | GSE39379 | GEO
Project description:Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to Dystrophin-expressing myofibers upon transplantation, a subset of which maintain Pax7 expression in vivo and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that iMPCs can be established from muscle tissue following small molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple differentiated cell types.
2018-05-01 | GSE108543 | GEO
Project description:Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to Dystrophin-expressing myofibers upon transplantation, a subset of which maintain Pax7 expression in vivo and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that iMPCs can be established from muscle tissue following small molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple differentiated cell types.
2018-05-01 | GSE92336 | GEO
Project description:(Abstract of publication submitted currently) To clarify molecular regulation of satellite cells, we performed genome-wide gene expression analysis of quiescent satellite cells isolated from mouse skeletal muscle by flow cytometry. We identified 53 novel quiescent satellite cell-specific genes whose expressions are sharply down-regulated upon activation. The gene list contains a number of cell surface molecules, transcriptional factors, and cytokines and other signal transduction molecules. We further confirmed that Odz4 and calcitonin receptor proteins were expressed by quiescent but not by activated satellite cells in vivo. Importantly, we found that Pax7+/calcitonin receptor+ satellite cells reappear in close association with regenerating myofibers 7 days after muscle damage, often outside the basal lamina. Moreover, an agonist of calcitonin receptor suppressed the activation of quiescent satellite cells on myofibers in in vitro culture, suggesting that calcitonin receptor signaling plays an important role in renewal and maintenance of satellite cells. Our results show the gene expression profile of quiescent satellite cells for the first time and reveal the temporal and spatial reappearance of a satellite cell pool. Experiment Overall Design: Satellite cells and non-satellite cells were examined. Totally three types of cells (groups), the satellite cells in quiescent and activated states and the non-satellite cells, were compared. Each has 4 replicates.
2008-06-12 | E-GEOD-3483 | biostudies-arrayexpress
Project description:Skeletal muscle stem cells, or satellite cells (SCs), are essential to regenerate and maintain muscle. Quiescent SCs reside in an asymmetric niche between the basal lamina and myofiber membrane. To repair muscle, SCs activate, proliferate, and differentiate, fusing to repair myofibers or reacquiring quiescence to replenish the SC niche. Little is known about when SCs reacquire quiescence during regeneration or the cellular processes that direct SC fate decisions and progression through myogenesis. Single cell sequencing of myogenic cells in regenerating muscle identifies SCs reacquiring quiescence and reveals that non-cell autonomous signaling networks influence SC fate decisions during regeneration. Single cell RNA-sequencing of regenerating skeletal muscle reveals that RBP expression, including numerous neuromuscular disease-associated RBPs, is temporally regulated in skeletal muscle stem cells and correlates to stages of myogenic differentiation. By combining machine learning with RBP engagement scoring, we discover that the neuromuscular disease associated RBP Hnrnpa2b1 is a differentiation-specifying regulator of myogenesis controlling myogenic cell fate transitions during terminal differentiation.
2022-06-11 | GSE205690 | GEO
Project description:MicroRNAs (miRNAs) are important in the regulation of many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. In mature murine tibialis anterior muscle following injury, 298 miRNAs were significantly changed during the time course of muscle regeneration including 86 that were altered greater than 10-fold as compared to uninjured muscle. Temporal miRNA expression patterns were identified and included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a and -499) that were abruptly decreased following injury and then up-regulated in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration. This included miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition of MPC into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during skeletal muscle regeneration has been identified, i.e., miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. Skeletal muscles are damaged and repaired repeatedly throughout life. Muscle regeneration maintains locomotor function during aging and delays the appearance of clinical symptoms in neuromuscular diseases, such as Duchenne muscular dystrophy. The capacity for skeletal muscle growth and regeneration is conferred by satellite cells located between the basal lamina and the sarcolemma of mature myofibers. Upon injury, satellite cells reenter the cell cycle, proliferate, and then exit the cell cycle either to renew the quiescent satellite cell pool or to differentiate into mature myofibers. Despite recent advances, genes involved in these processes are still largely unknown. Understanding the molecular mechanisms that regulate satellite cell activities could promote development of novel countermeasures to enhance muscle regeneration that is compromised by diseases or aging. Using a muscle injury mouse model, we profiled miRNA expression during muscle regeneration.
2012-04-24 | E-GEOD-37479 | biostudies-arrayexpress
Project description:Identification of the gene targets of the SIX transcription factors in myogenic stem cells and in whole back muscles during murine fetal development Pax7 expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the Sine oculis homeobox related Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior (TA) muscle. Mutant stem cells form hypotrophic myofibers that are not innervated but retain the ability to self-renew.
2020-10-07 | GSE159079 | GEO