Gene expression profiling on innervated and denervated muscles of Smad4 KO and control mice.
Transcriptomics Dataset
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General Information
AccessionGSE49826
TitleGene expression profiling on innervated and denervated muscles of Smad4 KO and control mice.
DescriptionTo identify novel atrophy-related genes, which are controlled by BMP signaling, we performed gene expression profiling on innervated and 14 days denervated muscles of Smad4 knockout and control mice, focusing on genes that were differentially upregulated in denervated Smad4-/- muscles compared to controls. Among the different genes our attention was attracted by a gene that encodes for a novel f-box protein (Fbxo30) belonging to the SCF complex family of the ubiquitin ligases. Cell size is determined by the balance between protein synthesis and degradation. This equilibrium is affected by hormones, nutrients, energy levels, mechanical stress and cytokines. Mutations that inactivate Myostatin lead to important muscle growth in animals and humans. However, the signals and pathways responsible for this hypertrophy remain largely unknown. Here we find that BMP signaling, acting through Smad1/5/8, is the fundamental hypertrophic signal. Inhibition of BMP signaling causes muscle atrophy, abolishes the hypertrophic phenotype of Myostatin knockout and strongly exacerbates the effects of denervation and fasting. BMP-Smad1/5/8 negatively regulates a novel gene (Fbxo30) that encodes an ubiquitin ligase, that is required for muscle loss. Collectively, these data identify a critical role for the BMP pathway in adult muscle maintenance, growth and atrophy.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49826
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic SMAD4 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse SMAD4 KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in SMAD4 KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in SMAD4 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in SMAD4 KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in SMAD4 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in SMAD4 KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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