The human skeletal muscle transcriptome: Sex differences, alternative splicing, and tissue homogeneity assessed with RNA sequencing

FASEB Journal

Volumn 28, Issue 10, 2014, Pages 4571-4581

  Lindholm, Malene E ^a   Huss, Mikael ^b   Solnestam, Beata W ^b   Kjellqvist, Sanela ^b   Lundeberg, Joakim ^b   Sundberg, Carl J ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b SCIENCE FOR LIFE LABORATORY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA ACTIN; CITRATE SYNTHASE; CREATINE KINASE; ESTRADIOL; FRUCTOSE BISPHOSPHATE ALDOLASE; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; INITIATION FACTOR 2ALPHA; MESSENGER RNA; MYOSIN LIGHT CHAIN 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEASOME; PROTEIN P53; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; RNA ISOFORM; TRANSCRIPTOME; TROPOMYOSIN; TROPONIN;

ADULT; AEROBIC METABOLISM; ALTERNATIVE RNA SPLICING; ARTICLE; CELL RESPIRATION; CLINICAL ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FATTY ACID METABOLISM; FEMALE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENETIC ASSOCIATION; HISTOGRAM; HUMAN; HUMAN GENOME; HUMAN TISSUE; MALE; MUSCLE BIOPSY; PROTEOMICS; REAL TIME POLYMERASE CHAIN REACTION; RESPIRATORY CHAIN; RNA SEQUENCE; SEX DIFFERENCE; SKELETAL MUSCLE; VASTUS LATERALIS MUSCLE; Y CHROMOSOME; ANTIBODY SPECIFICITY; METABOLISM; SEQUENCE ANALYSIS;

ADULT; ALTERNATIVE SPLICING; FEMALE; HUMANS; MALE; MUSCLE, SKELETAL; ORGAN SPECIFICITY; SEQUENCE ANALYSIS, RNA; SEX FACTORS; TRANSCRIPTOME;

EID: 84907688003     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.14-255000     Document Type: Article

References (68)

1. Timmons, J. A., Jansson, E., Fischer, H., Gustafsson, T., Greenhaff, P. L., Ridden, J., Rachman, J., and Sundberg, C. J. (2005) Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans. BMC Biol. 3, 19
2. Malm, C., Nyberg, P., Engstrom, M., Sjodin, B., Lenkei, R., Ekblom, B., and Lundberg, I. (2000) Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies. J. Physiol. 529, 243-262
3. Little, J. P., Safdar, A., Cermak, N., Tarnopolsky, M. A., and Gibala, M. J. (2010) Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. Am J. Physiol. Regul. Integr. Comp. Physiol. 298, R912-R917
4. Mahoney, D. J., Parise, G., Melov, S., Safdar, A., and Tarnopolsky, M. A. (2005) Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J. 19, 1498-1500
5. Gordon, P. M., Liu, D., Sartor, M. A., IglayReger, H. B., Pistilli, E. E., Gutmann, L., Nader, G. A., and Hoffman, E. P. (2012) Resistance exercise training influences skeletal muscle immune activation: a microarray analysis. J. Appl. Physiol. 112, 443-453
6. Roth, S. M., Ferrell, R. E., Peters, D. G., Metter, E. J., Hurley, B. F., and Rogers, M. A. (2002) Influence of age, sex, and strength training on human muscle gene expression determined by microarray. Physiol. Genomics 10, 181-190
7. Gustafsson, T., Osterlund, T., Flanagan, J. N., von Walden, F., Trappe, T. A., Linnehan, R. M., and Tesch, P. A. (2010) Effects of 3 days unloading on molecular regulators of muscle size in humans. J. Appl. Physiol. (1985) 109, 721-727
8. Dalla Libera, L., Ravara, B., Gobbo, V., Tarricone, E., Vitadello, M., Biolo, G., Vescovo, G., and Gorza, L. (2009) A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle. J. Appl. Physiol. 107, 549-557
9. Sreekumar, R., Halvatsiotis, P., Schimke, J. C., and Nair, K. S. (2002) Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 51, 1913-1920
10. Olsson, A. H., Ronn, T., Elgzyri, T., Hansson, O., Eriksson, K. F., Groop, L., Vaag, A., Poulsen, P., and Ling, C. (2011) The expression of myosin heavy chain (MHC) genes in human skeletal muscle is related to metabolic characteristics involved in the pathogenesis of type 2 diabetes. Mol. Genet. Metab. 103, 275-281
11. Kulkarni, S. S., Salehzadeh, F., Fritz, T., Zierath, J. R., Krook, A., and Osler, M. E. (2012) Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus. Metabolism 61, 175-185
12. Baron, D., Magot, A., Ramstein, G., Steenman, M., Fayet, G., Chevalier, C., Jourdon, P., Houlgatte, R., Savagner, F., and Pereon, Y. (2011) Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle. PLoS One 6, e26952
13. Noguchi, S., Tsukahara, T., Fujita, M., Kurokawa, R., Tachikawa, M., Toda, T., Tsujimoto, A., Arahata, K., and Nishino, I. (2003) cDNA microarray analysis of individual Duchenne muscular dystrophy patients. Hum. Mol. Genet. 12, 595-600
14. Melia, M. J., Kubota, A., Ortolano, S., Vilchez, J. J., Gamez, J., Tanji, K., Bonilla, E., Palenzuela, L., Fernandez-Cadenas, I., Pristoupilova, A., Garcia-Arumi, E., Andreu, A. L., Navarro, C., Hirano, M., and Marti, R. (2013) Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene. Brain 136, 1508-1517
15. Millino, C., Fanin, M., Vettori, A., Laveder, P., Mostacciuolo, M. L., Angelini, C., and Lanfranchi, G. (2009) Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy. BMC Med 7, 14
16. Reardon, K. A., Davis, J., Kapsa, R. M., Choong, P., and Byrne, E. (2001) Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy. Muscle Nerve 24, 893-899
17. Khal, J., Hine, A. V., Fearon, K. C., Dejong, C. H., and Tisdale, M. J. (2005) Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int. J. Biochem. Cell Biol. 37, 2196-2206
18. Crimi, M., Bordoni, A., Menozzi, G., Riva, L., Fortunato, F., Galbiati, S., Del Bo, R., Pozzoli, U., Bresolin, N., and Comi, G. P. (2005) Skeletal muscle gene expression profiling in mitochondrial disorders. FASEB J. 19, 866-868
19. Larrouy, D., Barbe, P., Valle, C., Dejean, S., Pelloux, V., Thalamas, C., Bastard, J. P., Le Bouil, A., Diquet, B., Clement, K., Langin, D., and Viguerie, N. (2008) Gene expression profiling of human skeletal muscle in response to stabilized weight loss. Am. J. Clin. Nutr. 88, 125-132
20. Black, D. L. (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72, 291-336
21. Kornblihtt, A. R., Schor, I. E., Allo, M., Dujardin, G., Petrillo, E., and Munoz, M. J. (2013) Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat. Rev. Mol. Cell Biol. 14, 153-165
22. Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., and Burge, C. B. (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456, 470-476
23. Blekhman, R., Marioni, J. C., Zumbo, P., Stephens, M., and Gilad, Y. (2010) Sex-specific and lineage-specific alternative splicing in primates. Genome Res. 20, 180-189
24. Su, W. L., Modrek, B., GuhaThakurta, D., Edwards, S., Shah, J. K., Kulkarni, A. V., Russell, A., Schadt, E. E., Johnson, J. M., and Castle, J. C. (2008) Exon and junction microarrays detect widespread mouse strain-and sex-bias expression differences. BMC Genomics 9, 273
25. Hartmann, B., Castelo, R., Minana, B., Peden, E., Blanchette, M., Rio, D. C., Singh, R., and Valcarcel, J. (2011) Distinct regulatory programs establish widespread sex-specific alternative splicing in Drosophila melanogaster. RNA 17, 453-468
26. Maher, A. C., Fu, M. H., Isfort, R. J., Varbanov, A. R., Qu, X. A., and Tarnopolsky, M. A. (2009) Sex differences in global mRNA content of human skeletal muscle. PLoS One 4, e6335
27. Welle, S., Tawil, R., and Thornton, C. A. (2008) Sex-related differences in gene expression in human skeletal muscle. PLoS One 3, e1385
28. Liu, D., Sartor, M. A., Nader, G. A., Gutmann, L., Treutelaar, M. K., Pistilli, E. E., Iglayreger, H. B., Burant, C. F., Hoffman, E. P., and Gordon, P. M. (2010) Skeletal muscle gene expression in response to resistance exercise: sex specific regulation. BMC Genomics 11, 659
29. Seip, R. L., and Semenkovich, C. F. (1998) Skeletal muscle lipoprotein lipase: molecular regulation and physiological effects in relation to exercise. Exerc. Sport Sci. Rev. 26, 191-218
30. Koval, J. A., DeFronzo, R. A., O'Doherty, R. M., Printz, R., Ardehali, H., Granner, D. K., and Mandarino, L. J. (1998) Regulation of hexokinase II activity and expression in human muscle by moderate exercise. Am. J. Physiol. 274, E304-E308
31. Kraniou, Y., Cameron-Smith, D., Misso, M., Collier, G., and Hargreaves, M. (2000) Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle. J. Appl. Physiol. (1985) 88, 794-796
32. Mahoney, D. J., Carey, K., Fu, M. H., Snow, R., Cameron-Smith, D., Parise, G., and Tarnopolsky, M. A. (2004) Real-time RT-PCR analysis of housekeeping genes in human skeletal muscle following acute exercise. Physiol. Genomics 18, 226-231
33. Norrbom, J., Sallstedt, E. K., Fischer, H., Sundberg, C. J., Rundqvist, H., and Gustafsson, T. (2011) Alternative splice variant PGC-1alpha-b is strongly induced by exercise in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 301, E1092-E1098
34. Lexell, J., Taylor, C., and Sjostrom, M. (1985) Analysis of sampling errors in biopsy techniques using data from whole muscle cross sections. J. Appl. Physiol. 59, 1228-1235
35. Lexell, J., and Taylor, C. C. (1989) Variability in muscle fibre areas in whole human quadriceps muscle: how much and why? Acta Physiol. Scand. 136, 561-568
36. Polgar, J., Johnson, M. A., Weightman, D., and Appleton, D. (1973) Data on fibre size in thirty-six human muscles: an autopsy study. J. Neurol. Sci. 19, 307-318
37. Punkt, K., Mehlhorn, H., and Hilbig, H. (1998) Region-and age-dependent variations of muscle fibre properties. Acta Histochem. 100, 37-58
38. Kohn, T. A., and Myburgh, K. H. (2007) Regional specialization of rat quadriceps myosin heavy chain isoforms occurring in distal to proximal parts of middle and deep regions is not mirrored by citrate synthase activity. J. Anat. 210, 8-18
39. Bergström, J. (1962) Muscle electrolytes in man. Scand. J. Clin. Lab. Invest. 14, 1-110
40. Stranneheim, H., Werne, B., Sherwood, E., and Lundeberg, J. (2011) Scalable transcriptome preparation for massive parallel sequencing. PLoS One 6, e21910
41. Trapnell, C., Pachter, L., and Salzberg, S. L. (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111
42. Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., and Pachter, L. (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511-515
43. Anders, S., and Huber, W. (2010) Differential expression analysis for sequence count data. Genome. Biol. 11, R106
44. Timmons, J. A., Knudsen, S., Rankinen, T., Koch, L. G., Sarzynski, M. A., Jensen, T., Keller, P., Scheele, C., Vollaard, N. B., Nielsen, S., Akerstrom, T., Macdougald, O. A., Jansson, E., Greenhaff, P. L., Tarnopolsky, M. A., van Loon, L. J., Pedersen, B. K., Sundberg, C. J., Wahlestedt, C., Britton, S. L., and Bouchard, C. (2010) Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J. Appl. Physiol. 108, 1487-1496
45. Quinlan, A. R., and Hall, I. M. (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841-842
46. Hangauer, M. J., Vaughn, I. W., and McManus, M. T. (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet. 9, e1003569
47. Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., and Haussler, D. (2002) The human genome browser at UCSC. Genome Res. 12, 996-1006
48. Branca, R. M., Orre, L. M., Johansson, H. J., Granholm, V., Huss, M., Perez-Bercoff, A., Forshed, J., Kall, L., and Lehtio, J. (2014) HiRIEF LC-MS enables deep proteome coverage and unbiased proteogenomics. Nat. Methods 11, 69-52
49. Trygg, J., and Wold, S. (2002) Orthogonal projections to latent structures (O-PLS). J. Chemometr. 16, 119-128
50. Martens, H., Hoy, M., Westad, F., Folkenberg, B., and Martens, M. (2001) Analysis of designed experiments by stabilised PLS Regression and jack-knifing. Chemometr. Intell. Lab. Syst. 58, 151-170
51. Wold, S. (1978) Cross-validatory estimation of the number of components in factor and principal components models. Technometrics 20, 397-405
52. Kurtovic, S., Paloschi, V., Folkersen, L., Gottfries, J., Franco-Cereceda, A., and Eriksson, P. (2011) Diverging alternative splicing fingerprints in the transforming growth factor-beta signaling pathway identified in thoracic aortic aneurysms. Mol. Med. 17, 665-675
53. Kjellqvist, S., Maleki, S., Olsson, T., Chwastyniak, M., Branca, R. M., Lehtio, J., Pinet, F., Franco-Cereceda, A., and Eriksson, P. (2013) A combined proteomic and transcriptomic approach shows diverging molecular mechanisms in thoracic aortic aneurysm development in patients with tricuspid-and bicuspid aortic valve. Mol. Cell. Proteomics 12, 407-425
54. Lin, L., Sotonyi, P., Somogyi, E., Karlsson, J., Folkers, K., Nara, Y., Sylven, C., Kaijser, L., and Jansson, E. (1988) Coenzyme Q10 content in different parts of the normal human heart. Clin. Physiol. 8, 391-398
55. Chopard, A., Lecunff, M., Danger, R., Lamirault, G., Bihouee, A., Teusan, R., Jasmin, B. J., Marini, J. F., and Leger, J. J. (2009) Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures. Physiol. Genomics 38, 291-302
56. Ramskold, D., Wang, E. T., Burge, C. B., and Sandberg, R. (2009) An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLoS Comput. Biol. 5, e1000598
57. Lundby, C., Nordsborg, N., Kusuhara, K., Kristensen, K. M., Neufer, P. D., and Pilegaard, H. (2005) Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies. Eur. J. Appl. Physiol. 95, 351-360
58. Vissing, K., Andersen, J. L., and Schjerling, P. (2005) Are exercise-induced genes induced by exercise? FASEB J. 19, 94-96
59. Guerra, B., Gomez-Cabrera, M. C., Ponce-Gonzalez, J. G., Martinez-Bello, V. E., Guadalupe-Grau, A., Santana, A., Sebastia, V., Vina, J., and Calbet, J. A. (2011) Repeated muscle biopsies through a single skin incision do not elicit muscle signaling, but IL-6 mRNA and STAT3 phosphorylation increase in injured muscle. J. Appl. Physiol. (1985) 110, 1708-1715
60. Staron, R. S., Hagerman, F. C., Hikida, R. S., Murray, T. F., Hostler, D. P., Crill, M. T., Ragg, K. E., and Toma, K. (2000) Fiber type composition of the vastus lateralis muscle of young men and women. J. Histochem. Cytochem. 48, 623-629
61. Wang, M., Wang, X. C., Zhang, Z. Y., Mou, B., and Hu, R. M. (2010) Impaired mitochondrial oxidative phosphorylation in multiple insulin-sensitive tissues of humans with type 2 diabetes mellitus. J. Int. Med. Res. 38, 769-781
62. Thompson, J. R., Swanson, S. A., Casale, G. P., Johanning, J. M., Papoutsi, E., Koutakis, P., Miserlis, D., Zhu, Z., and Pipinos, I. I. (2013) Gastrocnemius mitochondrial respiration: are there any differences between men and women? J. Surg. Res. 185, 206-211
63. Costill, D. L., Daniels, J., Evans, W., Fink, W., Krahenbuhl, G., and Saltin, B. (1976) Skeletal muscle enzymes and fiber composition in male and female track athletes. J. Appl. Physiol. 40, 149-154
64. Seth, A., Steel, J. H., Nichol, D., Pocock, V., Kumaran, M. K., Fritah, A., Mobberley, M., Ryder, T. A., Rowlerson, A., Scott, J., Poutanen, M., White, R., and Parker, M. (2007) The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab. 6, 236-245
65. Mustonen, T., and Alitalo, K. (1995) Endothelial receptor tyrosine kinases involved in angiogenesis. J. Cell Biol. 129, 895-898
66. Kaipainen, A., Korhonen, J., Pajusola, K., Aprelikova, O., Persico, M. G., Terman, B. I., and Alitalo, K. (1993) The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells. J. Exp. Med. 178, 2077-2088
67. Kiens, B., Roepstorff, C., Glatz, J. F., Bonen, A., Schjerling, P., Knudsen, J., and Nielsen, J. N. (2004) Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle: influence of physical activity and gender. J. Appl. Physiol. (1985) 97, 1209-1218
68. Roepstorff, C., Donsmark, M., Thiele, M., Vistisen, B., Stewart, G., Vissing, K., Schjerling, P., Hardie, D. G., Galbo, H., and Kiens, B. (2006) Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise. Am. J. Physiol. Endocrinol. Metab. 291, E1106-E1114