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Circle-seq revealing eccDNA profiling of human bone marrow mesenchymal stem cells

ABSTRACT: 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,

ORGANISM(S): Homo sapiens

PROVIDER: GSE261856 | GEO | 2024/04/15

REPOSITORIES: GEO

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Whole-genome sequencing of Extrachromosomal circular DNA (eccDNA) of cerebrospinal fluid of Medulloblastoma

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

ATAC-seq identifies thousands of extrachromosomal circular DNA in cancers and cell lines

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

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

2023-07-02 | GSE235888 | GEO

Extrachromosomal circular DNAs are ubiquitous in mouse hearts and function as enhancers to promote chromosomal transcription [Circle-seq]

Project description:To systematically analyzed the genome-wide characterization of potential eccDNAs in mouse heart tissues, we peformed Circle-seq in embryonic, neonatal and adult mouse heart tissues.

2023-12-31 | GSE216956 | GEO

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [RNA-seq]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. Herein, we identified a set of SUZ12-containing eccDNAs in RB. Through multiomics analyses, we demonstrated that SUZ12 contributes to elevated levels of H3K27me3 modification and subsequently inhibits the transcription of KLF4 during the oncogenic progression of retinoblastoma. Conclusively, our study unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

2023-07-02 | GSE235887 | GEO

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [CUT&Tag]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. Herein, we identified a set of SUZ12-containing eccDNAs in RB. Through multiomics analyses, we demonstrated that SUZ12 contributes to elevated levels of H3K27me3 modification and subsequently inhibits the transcription of KLF4 during the oncogenic progression of retinoblastoma. Conclusively, our study unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

2023-08-05 | GSE239785 | GEO

Distinct circular DNA profile in hSOD1G93A ALS that intersects with ALS proteome changes

Project description:Numerous genes mutated in amyotrophic lateral sclerosis (ALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. DNA instability and repair mechanisms segregate extrachromosomal circular DNAs (ec/eccDNAs) that can modulate gene expression somatically. Here, circulome profiling in a hSOD1G93A genotoxicity model of ALS revealed a 6-fold enrichment of small-size eccDNAs relative to controls. DifCir-based differential analysis identified 189 genes with patterned segregation of differentially produced per gene circles (DPpGCs) from ALS but not from control samples, implicating an inter-sample recurrence rate of at least 89% for the top 6 DPpGCs. Mass spectrometry-based ALS circulome-proteome cross-referencing revealed 31 corresponding differentially expressed proteins (DEPs), with 12 DPpGC-DEP pairs being itemized in ALS risk GWAS databases. DPpGC-DEP hotspots mainly convey neuron-specific functions counteracting ALS detriments. This is unanticipated evidence for non-random, profiled eccDNA accumulation in ALS neurodegeneration, involving putative interactions with their gene products as well as biomarker perspectives.

2023-09-20 | GSE214718 | GEO

eccDNA biogenesis and its role in innate immunity

Project description:Extrachromosomal circular DNA elements (EccDNAs) have been described in the literature for several decades and are known for their wide existence across species as well as their high heterogeneity in genomic origins. Due to their scarcity and lack of validation tools, their biogenesis as well as their functions are largely unknown. Here, by using a newly developed circular DNA enrichment method, we purified eccDNAs from different cells and mapped their genomic location using both Illumine and Nanopore sequencing. We found that eccDNAs are mapped to genome in a largely random fashion, suggesting a biogenesis mechanism of random ligation of genomic DNA fragments. Consistently, we found that apoptosis inducers can increase the eccDNA generation, which is dependent on DNase 1/3 and DNA ligase 3. Importantly, we demonstrate that eccDNAs function as potent innate immunostimulants in a sequence-independent, but circularization-dependent fashion.

2021-08-05 | GSE165919 | GEO

Single-cell Circle-seq unveils diversity and cell specificity of circular DNA in single cells

Project description:Circular DNAs have been reported for decades and have been linked to tumorigenesis in humans. Previous sequencing-based genomic approaches capture circular DNA and average their readout over millions of cells, thereby losing insight into intercellular variation. Here, we introduce single-cell Circle-seq and show that the occurrence of most circular DNA species is stochastic, with some oncogene-containing large circular DNAs observed relatively frequently among different single cells. Despite this stochasticity, circular DNA is cell type-specific, which is concordant with H3K9me3 and H3K4me3 chromatin modification specificity of the corresponding cell lines. Moreover, we identify a cell type-specific circular DNA signature in cancer cells, which, we believe holds potential for early cancer diagnosis. In sum, our novel method single-cell Circle-seq dissects the randomness and cell type-specificity of circular DNAs at the single-cell level and uncovers the potential clinical application of circular DNA.

2024-01-02 | GSE221884 | GEO

Primary Neuroblastoma Circle-seq

Project description:We generated Circle-seq data for primary neuroblastoma to describe the landscape of extrachromosomal circular DNA in neuroblastoma.

| EGAS00001004797 | EGA

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