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Updated: Jul 9, 2025
Preparation of Adipose Progenitor Cells from Mouse Epididymal Adipose Tissues
Published on: August 25, 2020
Deciphering the role of extrachromosomal circular DNA in adipose stem cells from old and young donors
Sen Ren1, Du Wu1, Xiaoyong Shen2
1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Background:
The functional impairment of adipose stem cells (ASCs) during aging limits their clinical transformation. Studies have shown that extrachromosomal circular DNAs (eccDNAs) are associated with tumor progression and cell aging, but the roles of eccDNAs in ASCs remain unknown.
Method:
We conducted Circle sequencing (Circle-seq) to identify eccDNAs in ASCs isolated from young and old donors. The differentially expressed eccDNAs were calculated, annotated and validated via polymerase chain reaction.
Results:
Thousands of eccDNAs were identified and comprehensively characterized. Most of them were GC-rich, < 1000 base pairs in size, and were enriched on chromosome 19 and 17 with a high density of Alu elements and genes, 2 kb upstream/downstream of genes and satellites. In total, 3025 eccDNAs were differentially expressed among the two ASC groups. Conjoint analysis of the Circle-seq results and previous RNA-seq results revealed that 73 eccDNAs and 55 genes exhibited the same differential expression between the two groups. KEGG and GO analyses revealed that genes encoding differentially expressed eccDNAs were enriched for cell adhesion, cellular senescence and TGF-β receptor signaling pathway. We also found that aged ASCs exhibited loss of eccDNAs, including CAMK2G (chr10: 75577899-75578176), TRABD2B (chr1: 48305638-48307008) and TRABD2B (chr1: 48305425-48307091).
Conclusion:
In this study, we elucidated the first eccDNA profile relating to ASCs and demonstrated that three eccDNAs are lost in aged ASCs, which may be potential biomarkers of stem cell aging and valuable targets for stem cell rejuvenation.
Insights
Extrachromosomal circular DNAs (eccDNAs) were analyzed in aging adipose stem cells (ASCs). Aged ASCs showed a loss of specific eccDNAs, suggesting their potential as biomarkers for stem cell aging and rejuvenation targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Adipose stem cells (ASCs) show functional decline with age, limiting their therapeutic use.
- Extrachromosomal circular DNAs (eccDNAs) are implicated in aging and cancer, but their role in ASCs is unknown.
Purpose of the Study:
- To characterize eccDNAs in young versus aged ASCs.
- To identify potential eccDNA biomarkers for stem cell aging.
Main Methods:
- Circle sequencing (Circle-seq) was used to identify eccDNAs in ASCs from different age groups.
- Differential expression analysis and PCR validation were performed.
Main Results:
- Thousands of eccDNAs were identified, predominantly small and GC-rich, with specific chromosomal enrichments.
- 3025 eccDNAs showed differential expression between young and aged ASCs.
- Aged ASCs exhibited a loss of specific eccDNAs, including those associated with cell adhesion and senescence pathways.
Conclusions:
- This study presents the first eccDNA profile for ASCs.
- The loss of specific eccDNAs in aged ASCs may serve as biomarkers for stem cell aging.
- These eccDNAs could be targets for stem cell rejuvenation therapies.
