Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems.
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ID: 277884
2024
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Abstract
Understanding metabolic heterogeneity is the key to uncovering the underlying mechanisms of metabolic-related diseases. Current metabolic imaging studies suffer from limitations including low resolution and specificity, and the model systems utilized often lack human relevance. Here, we present a single-cell metabolic imaging platform to enable direct imaging of lipid metabolism with high specificity in various human-derived 2D and 3D culture systems. Through the incorporation of an azide-tagged infrared probe, selective detection of newly synthesized lipids in cells and tissue became possible, while simultaneous fluorescence imaging enabled cell-type identification in complex tissues. In proof-of-concept experiments, newly synthesized lipids were directly visualized in human-relevant model systems among different cell types, mutation status, differentiation stages, and over time. We identified upregulated lipid metabolism in progranulin-knockdown human induced pluripotent stem cells and in their differentiated microglia cells. Furthermore, we observed that neurons in brain organoids exhibited a significantly lower lipid metabolism compared to astrocytes.
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| Authors | Bai, Yeran;Camargo, Carolina M;Glasauer, Stella M K;Gifford, Raymond;Tian, Xinran;Longhini, Andrew P;Kosik, Kenneth S; |
| Journal | Nature communications |
| Year | 2024 |
| DOI |
350
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