| |  Online-Ressource |
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| Verfasst von: | Riegel, Dania [VerfasserIn]  |
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| | Romero-Fernández, Elena [VerfasserIn] |
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| | Simon, Malte [VerfasserIn] |
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| | Adenugba, Akinbami Raphael [VerfasserIn] |
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| | Singer, Katrin [VerfasserIn] |
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| | Mayr, Roman [VerfasserIn] |
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| | Weber, Florian [VerfasserIn] |
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| | Kleemann, Mark [VerfasserIn] |
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| | Imbusch, Charles [VerfasserIn] |
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| | Kreutz, Marina [VerfasserIn] |
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| | Brors, Benedikt [VerfasserIn] |
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| | Ugele, Ines [VerfasserIn] |
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| | Werner, Jens M. [VerfasserIn] |
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| | Siska, Peter J. [VerfasserIn] |
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| | Schmidl, Christian [VerfasserIn] |
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| Titel: | Integrated single-cell profiling dissects cell-state-specific enhancer landscapes of human tumor-infiltrating CD8+ T cells |
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| Verf.angabe: | Dania Riegel, Elena Romero-Fernández, Malte Simon, Akinbami Raphael Adenugba, Katrin Singer, Roman Mayr, Florian Weber, Mark Kleemann, Charles D. Imbusch, Marina Kreutz, Benedikt Brors, Ines Ugele, Jens M. Werner, Peter J. Siska, and Christian Schmidl |
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| E-Jahr: | 2023 |
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| Jahr: | 16 February 2023 |
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| Umfang: | 26 S. |
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| Fussnoten: | Online verfügbar 18. Januar 2023, Artikelversion 16. Februar 2023 ; Gesehen am 29.03.2023 ; Im Titel ist das Pluszeichen hochgestellt |
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| Titel Quelle: | Enthalten in: Molecular cell |
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| Ort Quelle: | [Cambridge, Mass.] : Cell Press, 1997 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 83(2023), 4 vom: Feb., Seite 622-636.e10 |
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| ISSN Quelle: | 1097-4164 |
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| Abstract: | Despite extensive studies on the chromatin landscape of exhausted T cells, the transcriptional wiring underlying the heterogeneous functional and dysfunctional states of human tumor-infiltrating lymphocytes (TILs) is incompletely understood. Here, we identify gene-regulatory landscapes in a wide breadth of functional and dysfunctional CD8+ TIL states covering four cancer entities using single-cell chromatin profiling. We map enhancer-promoter interactions in human TILs by integrating single-cell chromatin accessibility with single-cell RNA-seq data from tumor-entity-matching samples and prioritize cell-state-specific genes by super-enhancer analysis. Besides revealing entity-specific chromatin remodeling in exhausted TILs, our analyses identify a common chromatin trajectory to TIL dysfunction and determine key enhancers, transcriptional regulators, and deregulated genes involved in this process. Finally, we validate enhancer regulation at immunotherapeutically relevant loci by targeting non-coding regulatory elements with potent CRISPR activators and repressors. In summary, our study provides a framework for understanding and manipulating cell-state-specific gene-regulatory cues from human tumor-infiltrating lymphocytes. |
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| DOI: | doi:10.1016/j.molcel.2022.12.029 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.molcel.2022.12.029 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S1097276522012126 |
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| | DOI: https://doi.org/10.1016/j.molcel.2022.12.029 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | cancer immunology |
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| | chromatin accessibility |
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| | CRISPR activation |
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| | CRISPR interference |
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| | enhancer |
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| | gene regulation |
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| | single-cell ATAC-seq |
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| | T cell exhaustion |
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| | tumor-infiltrating T cells |
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| K10plus-PPN: | 1840464739 |
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| Verknüpfungen: | → Zeitschrift |
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Integrated single-cell profiling dissects cell-state-specific enhancer landscapes of human tumor-infiltrating CD8+ T cells / Riegel, Dania [VerfasserIn]; 16 February 2023 (Online-Ressource)
