Differential microRNA Expression during Muscle Regeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37479 | GEO | 2012/04/24
SECONDARY ACCESSION(S): PRJNA161505
REPOSITORIES: GEO
Similar Datasets
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:MicroRNAs (miRNAs) are important in the regulation of many biological processes such as growth and development. To evaluate the role of miRNAs in skeletal muscle regeneration, global miRNA expression was measured during muscle cell growth and differentiation. Primary cultures of murine myogenic progenitor cells (MPC) were studied for miRNA expression using quantitative PCR-array. During MPC differentiation or proliferation, 139 or 16 miRNAs, respectively, exhibited significant >2-fold changes. Cluster analysis revealed 5 distinct miRNA expression patterns at different stages of differentiation. Fourteen miRNAs exhibiting >10-fold change during differentiation included miR-1, 10b, 96, 98, 133a, 139-5p, 330, 335-3p, 339-5p, 344, 486, 499, 504, and 598. Ten of these miRNAs were located in introns of protein coding genes, such as miR-499 located in the myosin heavy chain isoform Myh7b. In silico analysis of possible miRNA-mRNA interactions indicated that many of these miRNAs targeted mRNA critically involved in muscle differentiation. Interestingly, several miRNAs targeted different sites in a given mRNA, suggesting coordinated expression of multiple miRNAs to ensure the regulation of essential genes. These results identify differentially expressed miRNAs that could represent new regulatory elements in MPC proliferation and differentiation. Myogenic progenitor cell (MPC) growth and differentiation are key elements duing muscle regeneration. Using defined culture conditions to promote proliferation or differentiation, we profiled miRNA expression in primary cultures of murine MPC.
2009-06-13 | E-GEOD-16473 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are important in the regulation of many biological processes such as growth and development. To evaluate the role of miRNAs in skeletal muscle regeneration, global miRNA expression was measured during muscle cell growth and differentiation. Primary cultures of murine myogenic progenitor cells (MPC) were studied for miRNA expression using quantitative PCR-array. During MPC differentiation or proliferation, 139 or 16 miRNAs, respectively, exhibited significant >2-fold changes. Cluster analysis revealed 5 distinct miRNA expression patterns at different stages of differentiation. Fourteen miRNAs exhibiting >10-fold change during differentiation included miR-1, 10b, 96, 98, 133a, 139-5p, 330, 335-3p, 339-5p, 344, 486, 499, 504, and 598. Ten of these miRNAs were located in introns of protein coding genes, such as miR-499 located in the myosin heavy chain isoform Myh7b. In silico analysis of possible miRNA-mRNA interactions indicated that many of these miRNAs targeted mRNA critically involved in muscle differentiation. Interestingly, several miRNAs targeted different sites in a given mRNA, suggesting coordinated expression of multiple miRNAs to ensure the regulation of essential genes. These results identify differentially expressed miRNAs that could represent new regulatory elements in MPC proliferation and differentiation.
2009-06-13 | GSE16473 | GEO
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir1_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110000 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir181_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110001 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir378_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110002 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir143_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110003.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110003 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mirs_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110004.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-09-26 | MODEL1704110004 | BioModels
Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.
2012-04-30 | E-GEOD-36077 | biostudies-arrayexpress
Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy.
2012-05-01 | GSE36077 | GEO