Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells
Abstract Introduction Skeletal muscle stem cells (MuSCs) have strong regenerative abilities, but as we age, their ability to regenerate decreases, leading to a decline in muscle function. Although the methylation reprogramming of super-enhancers (SEs) plays a pivotal role in regulating gene expressi...
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| Format: | Article |
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BMC
2025-08-01
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| Series: | Epigenetics & Chromatin |
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| Online Access: | https://doi.org/10.1186/s13072-025-00619-0 |
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| author | Anyu Zeng Hailong Liu Shuling He Xuming Luo Zhiqi Zhang Ming Fu Baoxi Yu |
| author_facet | Anyu Zeng Hailong Liu Shuling He Xuming Luo Zhiqi Zhang Ming Fu Baoxi Yu |
| author_sort | Anyu Zeng |
| collection | DOAJ |
| description | Abstract Introduction Skeletal muscle stem cells (MuSCs) have strong regenerative abilities, but as we age, their ability to regenerate decreases, leading to a decline in muscle function. Although the methylation reprogramming of super-enhancers (SEs) plays a pivotal role in regulating gene expression associated with the aging process, our understanding of the molecular diversity of stem cells during aging remains limited. This study aimed to identify the methylation profile of SEs in MuSCs and explore potential therapeutic molecular targets associated with aging. Methods The ROSE software was employed to identify super enhancers from the ChIP-seq data obtained from the ENCODE database. Additionally, the ALLCools and Methylpy packages were applied to analyze the methylation profile of SEs and to identify differentially methylated regions (DMRs) between aged and control samples using single-cell bisulfite sequencing (scBS-seq) data from the Gene Expression Omnibus (GEO) database. Overlap analysis was used to assess the regions of SEs and DMRs. The target genes and motifs were analyzed using KEGG, GO, and HOMER to identify key biological pathways and functions, followed by validation through snATAC-seq and immunofluorescence techniques. Results In conclusion, we conducted a multi-omics and cross-species analysis of MuSCs, creating a detailed methylation profile of SEs during aging. We identified key motifs and genes affected by SE methylation reprogramming, revealing important molecular pathways involved in aging. Notably, further analysis of the key gene PLXND1 revealed a decreasing expression trend in aged MuSCs, which appears to be linked to the hypermethylation of SE Rank 869. This epigenetic alteration is likely to contribute to the dysregulation of the SEMA3 signaling pathway, with profound implications for muscle regeneration in MuSCs during aging. Conclusion These findings suggest that epigenetic alterations in the methylation reprogramming of SEs are closely linked to the disruption of transcriptional networks during MuSCs aging. Moreover, our results offer valuable insights into the mechanisms driving SE methylation reprogramming, shedding light on how these epigenetic changes contribute to the molecular processes underlying aging. |
| format | Article |
| id | doaj-art-c44998b93f77488db361b900b1f8a950 |
| institution | Kabale University |
| issn | 1756-8935 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj-art-c44998b93f77488db361b900b1f8a9502025-08-20T03:46:15ZengBMCEpigenetics & Chromatin1756-89352025-08-0118111910.1186/s13072-025-00619-0Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cellsAnyu Zeng0Hailong Liu1Shuling He2Xuming Luo3Zhiqi Zhang4Ming Fu5Baoxi Yu6Department of Bone and Soft Tissue Surgery, Sun Yat-sen University Cancer CenterDepartment of Orthopaedics, Qilu Hospital of Shandong UniversityTraditional Chinese Medicine Prevention and Health Care Department, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese MedicineDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Joint Surgery, First Affiliated Hospital of Sun Yat-sen UniversityAbstract Introduction Skeletal muscle stem cells (MuSCs) have strong regenerative abilities, but as we age, their ability to regenerate decreases, leading to a decline in muscle function. Although the methylation reprogramming of super-enhancers (SEs) plays a pivotal role in regulating gene expression associated with the aging process, our understanding of the molecular diversity of stem cells during aging remains limited. This study aimed to identify the methylation profile of SEs in MuSCs and explore potential therapeutic molecular targets associated with aging. Methods The ROSE software was employed to identify super enhancers from the ChIP-seq data obtained from the ENCODE database. Additionally, the ALLCools and Methylpy packages were applied to analyze the methylation profile of SEs and to identify differentially methylated regions (DMRs) between aged and control samples using single-cell bisulfite sequencing (scBS-seq) data from the Gene Expression Omnibus (GEO) database. Overlap analysis was used to assess the regions of SEs and DMRs. The target genes and motifs were analyzed using KEGG, GO, and HOMER to identify key biological pathways and functions, followed by validation through snATAC-seq and immunofluorescence techniques. Results In conclusion, we conducted a multi-omics and cross-species analysis of MuSCs, creating a detailed methylation profile of SEs during aging. We identified key motifs and genes affected by SE methylation reprogramming, revealing important molecular pathways involved in aging. Notably, further analysis of the key gene PLXND1 revealed a decreasing expression trend in aged MuSCs, which appears to be linked to the hypermethylation of SE Rank 869. This epigenetic alteration is likely to contribute to the dysregulation of the SEMA3 signaling pathway, with profound implications for muscle regeneration in MuSCs during aging. Conclusion These findings suggest that epigenetic alterations in the methylation reprogramming of SEs are closely linked to the disruption of transcriptional networks during MuSCs aging. Moreover, our results offer valuable insights into the mechanisms driving SE methylation reprogramming, shedding light on how these epigenetic changes contribute to the molecular processes underlying aging.https://doi.org/10.1186/s13072-025-00619-0Super-enhancerMethylation reprogrammingSkeletal muscle stem cellAging |
| spellingShingle | Anyu Zeng Hailong Liu Shuling He Xuming Luo Zhiqi Zhang Ming Fu Baoxi Yu Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells Epigenetics & Chromatin Super-enhancer Methylation reprogramming Skeletal muscle stem cell Aging |
| title | Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells |
| title_full | Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells |
| title_fullStr | Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells |
| title_full_unstemmed | Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells |
| title_short | Multi-omic integration of single-cell data uncovers methylation profiles of super-enhancers in skeletal muscle stem cells |
| title_sort | multi omic integration of single cell data uncovers methylation profiles of super enhancers in skeletal muscle stem cells |
| topic | Super-enhancer Methylation reprogramming Skeletal muscle stem cell Aging |
| url | https://doi.org/10.1186/s13072-025-00619-0 |
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