CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation.
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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_DCE101C7865A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CD8+ T cell metabolic rewiring defined by scRNA-seq identifies a critical role of ASNS expression dynamics in T cell differentiation.
Journal
Cell reports
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
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
27/08/2024 6:32