Extrachromosomal circular DNAs are ubiquitous in mouse hearts and function as enhancers to promote chromosomal transcription [Circle-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216956 | GEO | 2023/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:Extrachromosomal circular DNAs (eccDNAs) are prevalent in different tumors, and have been shown to be important oncogenic drivers. While recent studies have found many eccDNAs in non-tumor cells, to date, the nature and characteristics of eccDNAs in human heart failure are rarely known. In this study, we provided a comprehensive analysis of eccDNAs in human heart failure caused by dilated cardiomyopathy (DCM). Using the Circle-Seq method, we identified the expression profile of eccDNAs in heart samples from DCM patients and healthy controls. Most eccDNAs were less than 1kb and enriched in two peaks. Analysis of the genomic distribution of eccDNAs revealed that eccDNAs were derived from all chromosomes and half of these eccDNAs carried at least one gene or gene fragment. Most eccDNAs originated from 5’UTR, 3’UTR, CpG island, long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). In addition, eccDNAs were more enriched on gene-rich chromosomes 17 and 19. In conclusion, our work delineated the eccDNAs profiling of human healthy heart and DCM and explored potential functions of eccDNAs in the development of DCM.
2024-12-31 | GSE241568 | GEO
Project description:To exaimine the transcription levels among embryonic, neonatal and adult mouse heart tissues, we performed the whole transcriptome sequencing.
2023-12-31 | GSE217077 | GEO
Project description:Extrachromosomal circular DNAs (eccDNAs) have been discovered in various species and play a significant role in cancer development However, our understanding of eccDNAs in normal cells is limited. Here, we conducted eccDNA sequencing by Circle-seq in undifferentiated human bone marrow mesenchymal stem cells (uhBMSCs) and their differentiation into osteoblasts (OBs), chondrocytes (CCs), and adipocytes (ACs) to gain knowledge about eccDNAs in cell differentiation,
2025-01-31 | GSE261856 | GEO
Project description:Extrachromosomal circular DNAs are ubiquitous in mouse hearts and function as enhancers to promote chromosomal transcription [Circle-seq]
| PRJNA896237 | ENA
Project description:Background: Medulloblastoma (MB) is one of the malignant tumors of the central nervous system (CNS) with a poor prognosis and lack of effective detection. Extrachromosomal circular DNA (eccDNA) has been reported to be closely related to CNS tumors. However, there is still a gap in eccDNA of MB.Methods: Genomic features of eccDNAs were identified in MB tissues and matched cerebrospinal fluid (CSF) using a circle-map, compared with normal. The nucleotides on both sides of the eccDNAs breakpoint were analyzed to investigate the mechanisms of eccDNAs formation. Bioinformatics analysis combined with the GEO database identified reliable features of eccDNA-related genes in MB. Lasso Cox regression model, univariate and multivariate Cox regression analysis, time-dependent ROC, and Kaplan–Meier curve were used to assess the potential diagnostic and prognostic value of the Hub genes.Results: 35179 eccDNAs were identified, with the majority less than 1000 base pairs (bp). The distribution of eccDNAs on the genome was closely related to gene density. EccDNAs in CSF exhibited phase parallelism with matched MB tissues and were shown differently in tumors and normal. Ten core genes were identified in combination with GEO and showed reliable diagnostic and prognostic value in independent datasets through univariate and multivariate Cox regression. Nomogram included Hub-gene signatures was established and showed clinical benefit.Conclusions: This study described the characteristics and formation mechanism of eccDNAs in MB and CSF. The role of eccDNA in MB was revealed, and eccDNA-associated hub genes in CSF could be used as diagnostic and prognostic biomarkers for MB.
2022-10-20 | GSE205178 | GEO
Project description:BackgroundExtrachromosomal circular deoxyribonucleic acid (eccDNA) is evolving as a valuable biomarker, while little is known about its presence in urine.MethodsHere, we report the discovery and analysis of urinary cell-free eccDNAs (ucf-eccDNAs) in healthy controls and patients with advanced chronic kidney disease (CKD) by Circle-Seq.ResultsMillions of unique ucf-eccDNAs were identified and comprehensively characterised. The ucf-eccDNAs are GC-rich. Most ucf-eccDNAs are less than 1000 bp and are enriched in four pronounced peaks at 207, 358, 553 and 732 bp. Analysis of the genomic distribution of ucf-eccDNAs shows that eccDNAs are found on all chromosomes but enriched on chromosomes 17, 19 and 20 with a high density of protein-coding genes, CpG islands, short interspersed transposable elements (SINEs) and simple repeat elements. Analysis of eccDNA junction sequences further suggests that microhomology and palindromic repeats might be involved in eccDNA formation. The ucf-eccDNAs in CKD patients are significantly higher than those in healthy controls. Moreover, eccDNA with miRNA genes is highly enriched in CKD ucf-eccDNA.ConclusionsThis work discovers and provides the first deep characterisation of ucf-eccDNAs and suggests ucf-eccDNA as a valuable noninnvasive biomarker for urogenital disorder diagnosis and monitoring.
| S-EPMC9042798 | biostudies-literature
Project description:Introduction: Extrachromosomal circular DNA (eccDNA) plays significant roles in cancer progression and prognosis. However, it remains unclear whether cell-free eccDNA, considered more stable than linear DNA, possesses cancer-specific genomic features. Furthermore, the biogenesis and function of eccDNAs are not yet fully understood. Objectives: This study aims to characterize the genomic landscape of urinary cell-free eccDNAs in prostate cancer (PCa) and non-cancer (NC) individuals, elucidate their biogenesis and PCa-specific genomic features, and investigate their roles in PCa progression. Methods: We conducted urine Circle-seq for 21 PCa patients and 16 NC individuals, performed integrated analysis with other omics datasets, and finally validated the function of eccDNA by in vitro transfection and RNA-seq. Results: We pioneered the profiling of urinary cell-free eccDNAs landscape in PCa and uncovered a high association between eccDNA generation and active chromatin status as well as gene transcription. Double strand breaks and R-loops, which preferentially occur in active genomic sites and cause genome instability, can promote eccDNA generation. Genome instability frequently results in genomic mutations, and our study further established a link between eccDNA generation and oncogenic mutations. Additionally, genes specifically exhibiting high eccDNA generation frequency (HFGs) in PCa contributed to PCa progression and were associated with poorer survival outcomes in PCa patients. Finally, we demonstrated that eccDNAs derived from PCa-specific HFGs, in contrast to intergenic eccDNAs, could suppress PCa cell proliferation and migration, which was independent of their host gene expression. Conclusion: Our study illustrated the biogenesis of eccDNAs from DSBs in active genes, revealed PCa-specific eccDNA features and suggested new mechanisms underlying eccDNA function.
2025-05-01 | GSE292750 | GEO
Project description:It has been verified that extrachromosomal circular DNA (ecDNA) has important clinical significance, and the formation process of ecDNA, its immunogenicity, and its other functions have also been described. However, the balancing mechanism by which cells respond to ecDNA, i.e., how ecDNA degrades within cells, is unclear. Here, by using Circle-Seq method conducted on PLC-PRF-5 HCC Cells, ecDNA was purified and the samples were used for DNA Library Preparation and Next Generation Paired-End Sequencing using Illumina MiSeq Technology, We found that some ecDNAs disappeared after VD treatment compared with the DMSO group, and these disappearing ecDNA were related to EMT, proliferation, cell cycle, focal adhesion and other malignant behaviors. Moreover, Circle-seq peaks narrowed after VD treatment, and the coverage over the whole gene was significantly reduced, suggesting that ecDNA after VD treatment carried smaller DNA fragments, which may cause them not to function as a whole gene. Importantly, we demonstrate that VD can cause a continuous and steady decrease in ecDNA in HCC cells.
2023-02-01 | GSE221428 | GEO
Project description:Extrachromosomal circular DNAs (eccDNAs) are usually somatically mosaic and a source of intercellular heterogeneity in normal and tumor cells. Because short eccDNAs are poorly chromatinized, we hypothesized that they are sequenced by tagmentation in ATAC-seq experiments, without any enrichment of circular DNA, and thus identified thousands of eccDNAs. The eccDNAs identified in cell lines were validated by inverse PCR on DNA that survives exonuclease digestion of linear DNA, and by metaphase FISH. ATAC-seq in Gliomas and Glioblastomas identify hundreds of eccDNAs, including one containing the well-known EGFR gene amplicon from chr7. Over 18,000 eccDNAs, many carrying known cancer driver genes, are identified in a pan-cancer analysis of 360 ATAC-seq libraries from 23 tumor types. Because of somatic mosaicism, eccDNAs are identified by ATAC-seq even before amplification of the locus is recognized by genome-wide copy number variation measurements. Thus, standard ATAC-seq is a sensitive method to detect eccDNA present in a subset of tumor cells, ready to be amplified under appropriate selection, as during therapy.
2020-02-18 | GSE145409 | GEO
Project description:The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently1. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division2,3. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells4. How multiple ecDNA species within a tumour cell are assorted and maintained across somatic cell generations is unclear. Here we show that cooperative ecDNA species are coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. ecDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy-number gains in multiple ecDNA species before any selection. Intermolecular proximity and active transcription at the start of mitosis facilitate the coordinated segregation of ecDNA species, and transcription inhibition reduces co-segregation. Computational modelling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations.
| S-EPMC11541006 | biostudies-literature