CD8<sup>+</sup> T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation.

Details

Serval ID
serval:BIB_DCE101C7865A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD8<sup>+</sup> T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation.
Journal
Cell reports
Author(s)
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.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
15/11/2022
Peer-reviewed
Oui
Volume
41
Number
7
Pages
111639
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
T cells dynamically rewire their metabolism during an immune response. We applied single-cell RNA sequencing to CD8 <sup>+</sup> 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 <sup>+</sup> T cells in a mouse melanoma model. We thus provide a resource of dynamic expression changes during CD8 <sup>+</sup> T cell activation and differentiation, and identify ASNS expression dynamics as a modulator of CD8 <sup>+</sup> T cell differentiation.
Keywords
Mice, Animals, CD8-Positive T-Lymphocytes, Single-Cell Analysis, Lymphocyte Activation, Cell Differentiation, Melanoma/metabolism, Disease Models, Animal, ASNS, CD8(+) T cells, CP: Immunology, T-cell activation, T-cell differentiation, asparagine, dynamics, immunology, metabolism, physiological media, scRNA-seq
Pubmed
Open Access
Yes
Create date
29/11/2022 8:44
Last modification date
04/01/2023 6:49
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