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Comparative gene expression profiling between cultured and tissue human skeletal muscle

ABSTRACT: Culturing myotubes from skeletal muscle (SM) biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies. We determined the transcriptomic differences between tissue and cultured SM samples from five individuals. In cultured myotubes compared to the tissue, 1216 genes were regulated: 583 down and 633 up. Downregulated genes were mainly associated with cytoplasm, particularly mitochondria, and involved in metabolism and the muscle-system/contraction process. Upregulated genes were predominantly related to cytoplasm, endoplasmic reticulum, and extracellular matrix. The most significantly regulated pathway was mitochondrial dysfunction. Apoptosis genes were also modulated. Among the most downregulated genes were genes encoding metabolic proteins AMPD1, PYGM, CPT1B and UCP3, muscle-system proteins TMOD4, MYBPC1, MYOZ1 and XIRP2, the proteolytic CAPN3 and the myogenic regulator MYF6. Within the most upregulated group were genes encoding senescence/apoptosis-related proteins CDKN1A and KIAA1199 and potential regulatory factors HIF1A, TOP2A and CCDC80. In conclusion, cultured muscle cells display reductive metabolic and muscle-system transcriptome adaptations as observed in muscle atrophy and they activate tissue-remodeling and senescence/apoptosis processes. Novel candidate regulators in SM dysfunction are revealed

ORGANISM(S): Homo sapiens

PROVIDER: GSE17503 | GEO | 2010/02/22

SECONDARY ACCESSION(S): PRJNA118915

REPOSITORIES: GEO

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Metabolic reprogramming during hyperammonemia targets mitochondrial function and post-mitotic senescence

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