Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue

BMC Genomics

Research Article

Anna M Gómez-Foix¹  Cèlia García-Martínez¹  Emma Mormeneo¹  Sylviane Métairon²  Martin Kussmann²  Frederic Raymond²  Jaume Colomer³  Andres Nascimento³ 

[1] CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Departament de Bioquímica i Biologia Molecular, IBUB, Facultat de Biologia, Universitat de Barcelona, 08028, Diagonal 645Barcelona, Spain;Nestlé Research Center, Vers-Chez-Les-Blanc, CH-1000, Lausanne 26, Switzerland;Unitat de Patologia Neuromuscular, Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain;

关键词: Skeletal Muscle;    Duchenne Muscular Dystrophy;    Ingenuity Pathway Analysis;    Downregulated Gene;    Skeletal Muscle Tissue;   

DOI  :  10.1186/1471-2164-11-125

 received in 2009-06-30, accepted in 2010-02-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundA high-sensitivity DNA microarray platform requiring nanograms of RNA input facilitates the application of transcriptome analysis to individual skeletal muscle (SM) tissue samples. Culturing myotubes from 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.ResultsWe used the Illumina expression BeadChips to determine the transcriptomic differences between tissue and cultured SM samples from five individuals. Changes in the expression of several genes were confirmed by QuantiGene Plex assay or reverse transcription real-time PCR. In cultured myotubes compared to the tissue, 1216 genes were regulated: 583 down and 633 up. Gene ontology analysis showed that 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 detected in this study 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. Coordinated reduced expression of five members of the GIMAP gene family, which form a cluster on chromosome 7, was shown, and the GIMAP4-reduction was validated. Within the most upregulated group were genes encoding senescence/apoptosis-related proteins CDKN1A and KIAA1199 and potential regulatory factors HIF1A, TOP2A and CCDC80.ConclusionsCultured muscle cells display reductive metabolic and muscle-system transcriptome adaptations as observed in muscle atrophy and they activate tissue-remodeling and senescence/apoptosis processes.

【 授权许可】

Unknown   
© Raymond et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.