Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA

Extrachromosomal circular DNA (eccDNA) is a special class of DNA derived from linear chromosomes. It coexists independently with linear chromosomes in the nucleus. eccDNA has been identified in multiple organisms, including Homo sapiens, and has been shown to play important roles relevant to tumor p...

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Main Authors: Jiajinlong Kang, Yulin Dai, Jinze Li, Huihui Fan, Zhongming Zhao
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2001037023000259
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author Jiajinlong Kang
Yulin Dai
Jinze Li
Huihui Fan
Zhongming Zhao
author_facet Jiajinlong Kang
Yulin Dai
Jinze Li
Huihui Fan
Zhongming Zhao
author_sort Jiajinlong Kang
collection DOAJ
description Extrachromosomal circular DNA (eccDNA) is a special class of DNA derived from linear chromosomes. It coexists independently with linear chromosomes in the nucleus. eccDNA has been identified in multiple organisms, including Homo sapiens, and has been shown to play important roles relevant to tumor progression and drug resistance. To date, computational tools developed for eccDNA detection are only applicable to bulk tissue. Investigating eccDNA at the single-cell level using a computational approach will elucidate the heterogeneous and cell-type-specific landscape of eccDNA within cellular context. Here, we performed the first eccDNA analysis at the single-cell level using data generated by single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) in adult and pediatric glioblastoma (GBM) samples. Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system with a poor prognosis. Our analysis provides an overview of cellular origins, genomic distribution, as well as the differential regulations between linear and circular genome under disease- and cell-type-specific conditions across the open chromatin regions in GBM. We focused on some eccDNA elements that are potential mobile enhancers acting in a trans-regulation manner. In summary, this pilot study revealed novel eccDNA features in the cellular context of brain tumor, supporting the strong need for eccDNA investigation at the single-cell level.
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spelling doaj.art-f08015f49c5a45788884a4644ce334902023-12-21T07:30:49ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012111151121Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNAJiajinlong Kang0Yulin Dai1Jinze Li2Huihui Fan3Zhongming Zhao4Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Epidemiology, Human Genetics, and Environment Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USACenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Correspondence to: Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St. Suite 600, Houston, TX 77030, USA.Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Department of Epidemiology, Human Genetics, and Environment Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Correspondence to: Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin St. Suite 600, Houston, TX 77030, USA.Extrachromosomal circular DNA (eccDNA) is a special class of DNA derived from linear chromosomes. It coexists independently with linear chromosomes in the nucleus. eccDNA has been identified in multiple organisms, including Homo sapiens, and has been shown to play important roles relevant to tumor progression and drug resistance. To date, computational tools developed for eccDNA detection are only applicable to bulk tissue. Investigating eccDNA at the single-cell level using a computational approach will elucidate the heterogeneous and cell-type-specific landscape of eccDNA within cellular context. Here, we performed the first eccDNA analysis at the single-cell level using data generated by single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) in adult and pediatric glioblastoma (GBM) samples. Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system with a poor prognosis. Our analysis provides an overview of cellular origins, genomic distribution, as well as the differential regulations between linear and circular genome under disease- and cell-type-specific conditions across the open chromatin regions in GBM. We focused on some eccDNA elements that are potential mobile enhancers acting in a trans-regulation manner. In summary, this pilot study revealed novel eccDNA features in the cellular context of brain tumor, supporting the strong need for eccDNA investigation at the single-cell level.http://www.sciencedirect.com/science/article/pii/S2001037023000259Single-cell ATAC sequencingGlioblastomaEc/eccDNADistal regulatorTransregulation
spellingShingle Jiajinlong Kang
Yulin Dai
Jinze Li
Huihui Fan
Zhongming Zhao
Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
Computational and Structural Biotechnology Journal
Single-cell ATAC sequencing
Glioblastoma
Ec/eccDNA
Distal regulator
Transregulation
title Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
title_full Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
title_fullStr Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
title_full_unstemmed Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
title_short Investigating cellular heterogeneity at the single-cell level by the flexible and mobile extrachromosomal circular DNA
title_sort investigating cellular heterogeneity at the single cell level by the flexible and mobile extrachromosomal circular dna
topic Single-cell ATAC sequencing
Glioblastoma
Ec/eccDNA
Distal regulator
Transregulation
url http://www.sciencedirect.com/science/article/pii/S2001037023000259
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