Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes
Abstract Background Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-018-1118-4 |
| _version_ | 1819152224322846720 |
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| author | Cajsa Davegårdh Elin Hall Wedin Christa Broholm Tora Ida Henriksen Maria Pedersen Bente Klarlund Pedersen Camilla Scheele Charlotte Ling |
| author_facet | Cajsa Davegårdh Elin Hall Wedin Christa Broholm Tora Ida Henriksen Maria Pedersen Bente Klarlund Pedersen Camilla Scheele Charlotte Ling |
| author_sort | Cajsa Davegårdh |
| collection | DOAJ |
| description | Abstract Background Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene expression in primary human myoblasts (activated satellite cells) before and after differentiation into myotubes. Method We used an array-based approach to analyse genome-wide DNA methylation and gene expression in myoblasts and myotubes from 13 women and 13 men. The results were followed up with a reporter gene assay. Results Genome-wide DNA methylation and gene expression differences between the sexes were detected in both myoblasts and myotubes, on the autosomes as well as the X-chromosome, despite lack of exposure to sex hormones and other factors that differ between sexes. Pathway analysis revealed higher expression of oxidative phosphorylation and other metabolic pathways in myoblasts from women compared to men. Oxidative phosphorylation was also enriched among genes with higher expression in myotubes from women. Forty genes in myoblasts and 9 in myotubes had differences in both DNA methylation and gene expression between the sexes, including LAMP2 and SIRT1 in myoblasts and KDM6A in myotubes. Furthermore, increased DNA methylation of LAMP2 promoter had negative effects on reporter gene expression. Five genes (CREB5, RPS4X, SYAP1, XIST, and ZRSR2) showed differential DNA methylation and gene expression between the sexes in both myoblasts and myotubes. Interestingly, differences in DNA methylation and expression between women and men were also found during differentiation (myoblasts versus myotubes), e.g., in genes involved in energy metabolism. Interestingly, more DNA methylation changes occur in women compared to men on autosomes. Conclusion All together, we show that epigenetic and transcriptional differences exist in human myoblasts and myotubes as well as during differentiation between women and men. We believe that these intrinsic differences might contribute to sex dependent differences in muscular phenotypes. |
| first_indexed | 2024-12-22T14:45:53Z |
| format | Article |
| id | doaj.art-49d48526969346c1a9737934f74b257f |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T14:45:53Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-49d48526969346c1a9737934f74b257f2022-12-21T18:22:27ZengBMCStem Cell Research & Therapy1757-65122019-01-0110111710.1186/s13287-018-1118-4Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubesCajsa Davegårdh0Elin Hall Wedin1Christa Broholm2Tora Ida Henriksen3Maria Pedersen4Bente Klarlund Pedersen5Camilla Scheele6Charlotte Ling7Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University HospitalDepartment of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University HospitalDepartment of Endocrinology, RigshospitaletDepartment of Endocrinology, RigshospitaletThe Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of CopenhagenThe Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of CopenhagenThe Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of CopenhagenDepartment of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University HospitalAbstract Background Sex differences are known to impact muscle phenotypes, metabolism, and disease risk. Skeletal muscle stem cells (satellite cells) are important for muscle repair and to maintain functional skeletal muscle. Here we studied, for the first time, effects of sex on DNA methylation and gene expression in primary human myoblasts (activated satellite cells) before and after differentiation into myotubes. Method We used an array-based approach to analyse genome-wide DNA methylation and gene expression in myoblasts and myotubes from 13 women and 13 men. The results were followed up with a reporter gene assay. Results Genome-wide DNA methylation and gene expression differences between the sexes were detected in both myoblasts and myotubes, on the autosomes as well as the X-chromosome, despite lack of exposure to sex hormones and other factors that differ between sexes. Pathway analysis revealed higher expression of oxidative phosphorylation and other metabolic pathways in myoblasts from women compared to men. Oxidative phosphorylation was also enriched among genes with higher expression in myotubes from women. Forty genes in myoblasts and 9 in myotubes had differences in both DNA methylation and gene expression between the sexes, including LAMP2 and SIRT1 in myoblasts and KDM6A in myotubes. Furthermore, increased DNA methylation of LAMP2 promoter had negative effects on reporter gene expression. Five genes (CREB5, RPS4X, SYAP1, XIST, and ZRSR2) showed differential DNA methylation and gene expression between the sexes in both myoblasts and myotubes. Interestingly, differences in DNA methylation and expression between women and men were also found during differentiation (myoblasts versus myotubes), e.g., in genes involved in energy metabolism. Interestingly, more DNA methylation changes occur in women compared to men on autosomes. Conclusion All together, we show that epigenetic and transcriptional differences exist in human myoblasts and myotubes as well as during differentiation between women and men. We believe that these intrinsic differences might contribute to sex dependent differences in muscular phenotypes.http://link.springer.com/article/10.1186/s13287-018-1118-4GenderMuscle stem cellsMyoblastsMyotubesSkeletal muscleEpigenetics |
| spellingShingle | Cajsa Davegårdh Elin Hall Wedin Christa Broholm Tora Ida Henriksen Maria Pedersen Bente Klarlund Pedersen Camilla Scheele Charlotte Ling Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes Stem Cell Research & Therapy Gender Muscle stem cells Myoblasts Myotubes Skeletal muscle Epigenetics |
| title | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| title_full | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| title_fullStr | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| title_full_unstemmed | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| title_short | Sex influences DNA methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| title_sort | sex influences dna methylation and gene expression in human skeletal muscle myoblasts and myotubes |
| topic | Gender Muscle stem cells Myoblasts Myotubes Skeletal muscle Epigenetics |
| url | http://link.springer.com/article/10.1186/s13287-018-1118-4 |
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