Journal Article

DZNE-2026-00189

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.

Toda Robert, A. ; McQuade, A. ; Koppes-den Hertog, S. J. ; Erlebach, L.DZNE* ; Kronenberg-Versteeg, D.DZNE* ; Kampmann, M. ; Giera, M. ; van der Kant, R.

2026
Cell Press Maryland Heights, MO

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Please use a persistent id in citations: doi:10.1016/j.stemcr.2025.102779

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.

Keyword(s): Microglia: metabolism (MeSH) ; Microglia: cytology (MeSH) ; Microglia: drug effects (MeSH) ; Microglia: immunology (MeSH) ; Induced Pluripotent Stem Cells: cytology (MeSH) ; Induced Pluripotent Stem Cells: metabolism (MeSH) ; Induced Pluripotent Stem Cells: drug effects (MeSH) ; Humans (MeSH) ; Lipidomics: methods (MeSH) ; Lipid Droplets: metabolism (MeSH) ; Culture Media: chemistry (MeSH) ; Culture Media: pharmacology (MeSH) ; Cell Differentiation: drug effects (MeSH) ; Lipid Metabolism (MeSH) ; Triglycerides: metabolism (MeSH) ; Cells, Cultured (MeSH) ; iPSC ; lipid droplet ; lipid metabolism ; lipidomics ; microglia ; neuroinflammation ; triglycerides ; Culture Media ; Triglycerides

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Contributing Institute(s):

1. Cell Biology of Neurological Diseases (AG Jucker)
2. Glial Cell Biology (AG Kronenberg-Versteeg)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 351 - Brain Function (POF4-351) (POF4-351)

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; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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