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| Status |
Public on Apr 07, 2015 |
| Title |
RNA-sequencing of healthy human skeletal myocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Skeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D.
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| Overall design |
Isolated skeletal muscle precursor cells from six normal glucose tolerant and non-obese males and females were differentiated in vitro. RNA from fully differentiated myotubes was sequenced using RNA-seq.
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| Contributor(s) |
Väremo L, Scheele C, Broholm C, Mardinoglu A, Kampf C, Asplund A, Nookaew I, Uhlén M, Klarlund Pedersen B, Nielsen J |
| Citation(s) |
25937284, 28545587 |
| Submission date |
Dec 05, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Leif Väremo |
| Organization name |
Chalmers University of Technology
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| Department |
Biology and Biological Engineering
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| Street address |
Kemivägen 10
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| City |
Gothenburg |
| ZIP/Postal code |
41296 |
| Country |
Sweden |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA269336 |
| SRA |
SRP050596 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63887_FPKM-values.txt.gz |
848.5 Kb |
(ftp)(http) |
TXT |
| GSE63887_RAW.tar |
1.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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