Title | Single-cell mapping of lipid metabolites using an infrared probe in human-derived model systems. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Bai Y, Camargo CM, Glasauer SMK, Gifford R, Tian X, Longhini AP, Kosik KS |
Journal | Nat Commun |
Volume | 15 |
Issue | 1 |
Pagination | 350 |
Date Published | 2024 Jan 08 |
ISSN | 2041-1723 |
Keywords | Astrocytes, Azides, Brain, Humans, Induced Pluripotent Stem Cells, Lipids |
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. |
DOI | 10.1038/s41467-023-44675-0 |
Alternate Journal | Nat Commun |
PubMed ID | 38191490 |
PubMed Central ID | PMC10774263 |
Grant List | P30 AG066444 / AG / NIA NIH HHS / United States U54 NS100717 / NS / NINDS NIH HHS / United States P01 AG026276 / AG / NIA NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States |