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Single-cell metabolic profiling of human cytotoxic T cells
Cellular metabolism regulates immune cell activation, differentiation and effector functions but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. Here, we developed an approach to characterize the metabolic regulome of single cells tog...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878201/ https://www.ncbi.nlm.nih.gov/pubmed/32868913 http://dx.doi.org/10.1038/s41587-020-0651-8 |
Sumario: | Cellular metabolism regulates immune cell activation, differentiation and effector functions but current metabolic approaches lack single-cell resolution and simultaneous characterization of cellular phenotype. Here, we developed an approach to characterize the metabolic regulome of single cells together with their phenotypic identity. The method, single-cell metabolic regulome profiling (scMEP), quantifies proteins that regulate metabolic pathway activity using a high-dimensional antibody-based approach. We employed mass cytometry (CyTOF) to benchmark scMEP against bulk metabolic assays by reconstructing the metabolic remodeling of in vitro-activated naïve and memory CD8(+) T cells. We applied the approach to clinical samples and identified tissue-restricted, metabolically repressed cytotoxic T cells in human colorectal carcinoma. Combining our method with imaging mass spectrometry (MIBI-TOF), we uncovered the spatial organization of metabolic programs, which indicated exclusion of metabolically repressed immune cells from the tumor-immune boundary. Overall, our approach enables robust approximation of metabolic and functional states in individual cells. |
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