Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems

Yeran Bai (), Carolina M. Camargo, Stella M. K. Glasauer, Raymond Gifford, Xinran Tian, Andrew P. Longhini and Kenneth S. Kosik ()
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Yeran Bai: University of California
Carolina M. Camargo: University of California
Stella M. K. Glasauer: University of California
Raymond Gifford: University of California
Xinran Tian: University of California
Andrew P. Longhini: University of California
Kenneth S. Kosik: University of California

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44675-0

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