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GTAC enables parallel genotyping of multiple genomic loci with chromatin accessibility profiling in single cells.
Turkalj, Sven; Jakobsen, Niels Asger; Groom, Angus; Metzner, Marlen; Riva, Simone G; Gür, E Ravza; Usukhbayar, Batchimeg; Salazar, Mirian Angulo; Hentges, Lance D; Mickute, Gerda; Clark, Kevin; Sopp, Paul; Davies, James O J; Hughes, Jim R; Vyas, Paresh.
Afiliação
  • Turkalj S; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Jakobsen NA; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Groom A; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Metzner M; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Riva SG; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Gür ER; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Usukhbayar B; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Salazar MA; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Hentges LD; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Mickute G; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Clark K; Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Sopp P; Flow Cytometry Facility, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Davies JOJ; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Hughes JR; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • Vyas P; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Oxford Centre for Haematology, NIHR Oxford Biomedical Research Centre, Oxford, UK; Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic add
Cell Stem Cell ; 30(5): 722-740.e11, 2023 05 04.
Article em En | MEDLINE | ID: mdl-37146586
ABSTRACT
Understanding clonal evolution and cancer development requires experimental approaches for characterizing the consequences of somatic mutations on gene regulation. However, no methods currently exist that efficiently link high-content chromatin accessibility with high-confidence genotyping in single cells. To address this, we developed Genotyping with the Assay for Transposase-Accessible Chromatin (GTAC), enabling accurate mutation detection at multiple amplified loci, coupled with robust chromatin accessibility readout. We applied GTAC to primary acute myeloid leukemia, obtaining high-quality chromatin accessibility profiles and clonal identities for multiple mutations in 88% of cells. We traced chromatin variation throughout clonal evolution, showing the restriction of different clones to distinct differentiation stages. Furthermore, we identified switches in transcription factor motif accessibility associated with a specific combination of driver mutations, which biased transformed progenitors toward a leukemia stem cell-like chromatin state. GTAC is a powerful tool to study clonal heterogeneity across a wide spectrum of pre-malignant and neoplastic conditions.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Leucemia Mieloide Aguda Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Leucemia Mieloide Aguda Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article