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Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice.

Lee YS, Talbot CC, Lee SJ - Genom Data (2015)

Bottom Line: Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use.Hence, benefits of this approach should be weighed against these potential detrimental effects.Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015).

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD 21205, USA.

ABSTRACT
Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use. One potential concern is that in muscle degenerative diseases, inducing hypertrophy may increase stress on dystrophic fibers. Our study shows that blocking this pathway in dysferlin deficient mice results in early improvement in histopathology but ultimately accelerates muscle degeneration. Hence, benefits of this approach should be weighed against these potential detrimental effects. Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015). Our data sets have been deposited in the Gene Expression Omnibus (GEO) database (GSE62945) and are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62945. Our data provide a resource for exploring molecular mechanisms that are related to hypertrophy-induced, accelerated muscular degeneration in dysferlinopathy.

No MeSH data available.


Related in: MedlinePlus

QQ plots wherein one-way comparisons of transcriptome change are compared between different one-way comparisons. (a) “wt versus Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts that are up-regulated in ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc) are also up-regulated in Dysf−/− (versus wt). (b) “wt versus Dysf−/−” and “F66 versus F66;Dysf−/−”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). (c) “F66 versus F66;Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). As expected, the probe set representing Dysf transcripts shows reduced hybridization with RNA from Dysf−/− (versus wt), ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc), and F66;Dysf−/− (versus F66) muscles.
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f0010: QQ plots wherein one-way comparisons of transcriptome change are compared between different one-way comparisons. (a) “wt versus Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts that are up-regulated in ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc) are also up-regulated in Dysf−/− (versus wt). (b) “wt versus Dysf−/−” and “F66 versus F66;Dysf−/−”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). (c) “F66 versus F66;Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). As expected, the probe set representing Dysf transcripts shows reduced hybridization with RNA from Dysf−/− (versus wt), ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc), and F66;Dysf−/− (versus F66) muscles.

Mentions: Microarray data were visualized by principal components analysis (PCA) mapping, volcano plots, and heat maps [6]. PCA analysis was performed with the Partek platform, while volcano plots and heat maps were generated with the Spotfire DecisionSite software (TIBCO Software Inc., Boston, MA). Linear regression analyses were performed with Spotfire to compare two different sets of transcriptome changes (Fig. 2). Gene Ontology (GO; www.geneontology.org) analysis was conducted for significantly differentially expressed 763 genes (fold change > 2.0, p < 0.01 in wt versus F66;Dysf−/−) using Spotfire's Gene Ontology Browser [7]. Canonical Pathways, Upstream Regulators, and Network analyses were generated using Ingenuity Pathway Analysis (IPA; QIAGEN Redwood City, CA, USA) and summarized in Table 1, Table 2, Table 3. Myostatin is a transforming growth factor-ß (TGF-ß) family member, and as expected, TGF-ß1 was a top upstream regulator in F66 mouse muscle (versus wt) (Fig. 3).


Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice.

Lee YS, Talbot CC, Lee SJ - Genom Data (2015)

QQ plots wherein one-way comparisons of transcriptome change are compared between different one-way comparisons. (a) “wt versus Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts that are up-regulated in ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc) are also up-regulated in Dysf−/− (versus wt). (b) “wt versus Dysf−/−” and “F66 versus F66;Dysf−/−”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). (c) “F66 versus F66;Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). As expected, the probe set representing Dysf transcripts shows reduced hybridization with RNA from Dysf−/− (versus wt), ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc), and F66;Dysf−/− (versus F66) muscles.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
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f0010: QQ plots wherein one-way comparisons of transcriptome change are compared between different one-way comparisons. (a) “wt versus Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts that are up-regulated in ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc) are also up-regulated in Dysf−/− (versus wt). (b) “wt versus Dysf−/−” and “F66 versus F66;Dysf−/−”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). (c) “F66 versus F66;Dysf−/−” and “wt with ACVR2B/Fc versus Dysf−/− with ACVR2B/Fc”: most of the transcripts are up-regulated only in F66;Dysf−/− (versus F66). As expected, the probe set representing Dysf transcripts shows reduced hybridization with RNA from Dysf−/− (versus wt), ACVR2B/Fc-injected Dysf−/− (versus wt with ACVR2B/Fc), and F66;Dysf−/− (versus F66) muscles.
Mentions: Microarray data were visualized by principal components analysis (PCA) mapping, volcano plots, and heat maps [6]. PCA analysis was performed with the Partek platform, while volcano plots and heat maps were generated with the Spotfire DecisionSite software (TIBCO Software Inc., Boston, MA). Linear regression analyses were performed with Spotfire to compare two different sets of transcriptome changes (Fig. 2). Gene Ontology (GO; www.geneontology.org) analysis was conducted for significantly differentially expressed 763 genes (fold change > 2.0, p < 0.01 in wt versus F66;Dysf−/−) using Spotfire's Gene Ontology Browser [7]. Canonical Pathways, Upstream Regulators, and Network analyses were generated using Ingenuity Pathway Analysis (IPA; QIAGEN Redwood City, CA, USA) and summarized in Table 1, Table 2, Table 3. Myostatin is a transforming growth factor-ß (TGF-ß) family member, and as expected, TGF-ß1 was a top upstream regulator in F66 mouse muscle (versus wt) (Fig. 3).

Bottom Line: Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use.Hence, benefits of this approach should be weighed against these potential detrimental effects.Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015).

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD 21205, USA.

ABSTRACT
Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use. One potential concern is that in muscle degenerative diseases, inducing hypertrophy may increase stress on dystrophic fibers. Our study shows that blocking this pathway in dysferlin deficient mice results in early improvement in histopathology but ultimately accelerates muscle degeneration. Hence, benefits of this approach should be weighed against these potential detrimental effects. Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015). Our data sets have been deposited in the Gene Expression Omnibus (GEO) database (GSE62945) and are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62945. Our data provide a resource for exploring molecular mechanisms that are related to hypertrophy-induced, accelerated muscular degeneration in dysferlinopathy.

No MeSH data available.


Related in: MedlinePlus