CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation
| Autor: | Juan Fernández-García, Fabien Franco, Sweta Parik, Patricia Altea-Manzano, Antonino Alejandro Pane, Dorien Broekaert, Joke van Elsen, Giusy Di Conza, Ines Vermeire, Tessa Schalley, Mélanie Planque, Thomas van Brussel, Rogier Schepers, Elodie Modave, Tobias K. Karakach, Peter Carmeliet, Diether Lambrechts, Ping-Chih Ho, Sarah-Maria Fendt |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Cell Reports Fernández-García, J, Franco, F, Parik, S, Altea-Manzano, P, Pane, A A, Broekaert, D, van Elsen, J, Vermeire, I, Schalley, T, Planque, M, van Brussel, T, Schepers, R, Modave, E, Karakach, T K, Carmeliet, P, Lambrechts, D, Ho, P C & Fendt, S M 2022, ' CD8 + T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation ', Cell Reports, vol. 41, no. 7, 111639 . https://doi.org/10.1016/j.celrep.2022.111639 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2022.111639 |
| Popis: | T cells dynamically rewire their metabolism during an immune response. We applied single-cell RNA sequencing to CD8+ T cells activated and differentiated in vitro in physiological medium to resolve these metabolic dynamics. We identify a differential time-dependent reliance of activating T cells on the synthesis versus uptake of various non-essential amino acids, which we corroborate with functional assays. We also identify metabolic genes that potentially dictate the outcome of T cell differentiation, by ranking them based on their expression dynamics. Among them, we find asparagine synthetase (Asns), whose expression peaks for effector T cells and decays toward memory formation. Disrupting these expression dynamics by ASNS overexpression promotes an effector phenotype, enhancing the anti-tumor response of adoptively transferred CD8+ T cells in a mouse melanoma model. We thus provide a resource of dynamic expression changes during CD8+ T cell activation and differentiation, and identify ASNS expression dynamics as a modulator of CD8+ T cell differentiation. ispartof: CELL REPORTS vol:41 issue:7 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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