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Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.

Aiko Toda Robert·Amanda McQuade·Sascha J Koppes-den Hertog·Lena Erlebach·Deborah Kronenberg-Versteeg·Martin Kampmann·Martin Giera·Rik van der Kant
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Abstract

Altered microglial lipid metabolism is heavily implicated in Alzheimer's disease (AD) and aging. Recently, protocols were developed to generate human induced pluripotent stem cell-derived microglia-like cells (iMGL) to study microglial function in vitro, including embryoid body-based methods and induced transcription factor (iTF)-dependent approaches. Here, we performed comparative lipidomics on iMGL from these methods and report major differences in multiple lipid classes, including triglycerides (TGs), a storage form of fatty acids implicated in microglial reactivity. TGs are strongly increased in iTF microglia due to the absence of a media supplement (B-27). Supplementing iTF microglia with B-27, or its component L-carnitine, reduces TGs and promotes a homeostatic state. B-27 also renders iTF microglia metabolically responsive to immune stimuli. Overall, our data show that iMGL differentiation methods have a major impact on microglial lipidomes and warrant attention when studying AD and neuroinflammatory processes involving lipids.

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MicrogliaHumansLipidomicsInduced Pluripotent Stem CellsLipid DropletsCell DifferentiationTriglyceridesLipid MetabolismCulture MediaiPSClipid dropletlipid metabolismlipidomicsmicroglianeuroinflammationtriglyceridesJournal ArticleComparative StudyResearch Support, Non-U.S. Gov't

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Aiko Toda Robert, Amanda McQuade, Sascha J Koppes-den Hertog, Lena Erlebach, Deborah Kronenberg-Versteeg, Martin Kampmann, Martin Giera, Rik van der Kant. 2026-01-08. Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.. https://doi.org/10.1016/j.stemcr.2025.102779

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