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Telomemore enables single-cell analysis of cell cycle and chromatin condensation
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0009-0003-5235-2999
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0002-9322-5879
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Department of Chemistry, Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic.ORCID iD: 0000-0002-5420-9702
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0003-2274-7343
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2025 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 53, no 3, article id gkaf031Article in journal (Refereed) Published
Abstract [en]

Single-cell RNA-seq methods can be used to delineate cell types and states at unprecedented resolution but do little to explain why certain genes are expressed. Single-cell ATAC-seq and multiome (ATAC + RNA) have emerged to give a complementary view of the cell state. It is however unclear what additional information can be extracted from ATAC-seq data besides transcription factor binding sites. Here, we show that ATAC-seq telomere-like reads counter-inituively cannot be used to infer telomere length, as they mostly originate from the subtelomere, but can be used as a biomarker for chromatin condensation. Using long-read sequencing, we further show that modern hyperactive Tn5 does not duplicate 9 bp of its target sequence, contrary to common belief. We provide a new tool, Telomemore, which can quantify nonaligning subtelomeric reads. By analyzing several public datasets and generating new multiome fibroblast and B-cell atlases, we show how this new readout can aid single-cell data interpretation. We show how drivers of condensation processes can be inferred, and how it complements common RNA-seq-based cell cycle inference, which fails for monocytes. Telomemore-based analysis of the condensation state is thus a valuable complement to the single-cell analysis toolbox.

Place, publisher, year, edition, pages
Oxford University Press, 2025. Vol. 53, no 3, article id gkaf031
National Category
Molecular Biology Medical Genetics and Genomics Medical Bioinformatics and Systems Biology
Identifiers
URN: urn:nbn:se:umu:diva-235667DOI: 10.1093/nar/gkaf031ISI: 001408073800005PubMedID: 39878215Scopus ID: 2-s2.0-85216776275OAI: oai:DiVA.org:umu-235667DiVA, id: diva2:1939742
Funder
Swedish National Infrastructure for Computing (SNIC)Swedish Research Council, 2021-06602Swedish Research Council, 2024-03952Swedish Cancer Society, 233102 PjThe Kempe Foundations, JCK-0055The Kempe Foundations, SMK-1959Knut and Alice Wallenberg Foundation, KAW 2020.0239Available from: 2025-02-24 Created: 2025-02-24 Last updated: 2025-02-24Bibliographically approved

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Yakovenko, IrynaMihai, Ionut SebastianSelinger, MartinRosenbaum, WilliamDernstedt, AndyGröning, RemigiusTrygg, JohanCarroll, LauraForsell, MattiasHenriksson, Johan

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Yakovenko, IrynaMihai, Ionut SebastianSelinger, MartinRosenbaum, WilliamDernstedt, AndyGröning, RemigiusTrygg, JohanCarroll, LauraForsell, MattiasHenriksson, Johan
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Molecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Department of Clinical MicrobiologyDepartment of Chemistry
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Nucleic Acids Research
Molecular BiologyMedical Genetics and GenomicsMedical Bioinformatics and Systems Biology

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