TY  - JOUR
AU  - Toda Robert, Aiko
AU  - McQuade, Amanda
AU  - Koppes-den Hertog, Sascha J
AU  - Erlebach, Lena
AU  - Kronenberg-Versteeg, Deborah
AU  - Kampmann, Martin
AU  - Giera, Martin
AU  - van der Kant, Rik
TI  - Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.
JO  - Stem cell reports
VL  - 21
IS  - 2
SN  - 2213-6711
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DZNE-2026-00189
SP  - 102779
PY  - 2026
AB  - 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.
KW  - Microglia: metabolism
KW  - Microglia: cytology
KW  - Microglia: drug effects
KW  - Microglia: immunology
KW  - Induced Pluripotent Stem Cells: cytology
KW  - Induced Pluripotent Stem Cells: metabolism
KW  - Induced Pluripotent Stem Cells: drug effects
KW  - Humans
KW  - Lipidomics: methods
KW  - Lipid Droplets: metabolism
KW  - Culture Media: chemistry
KW  - Culture Media: pharmacology
KW  - Cell Differentiation: drug effects
KW  - Lipid Metabolism
KW  - Triglycerides: metabolism
KW  - Cells, Cultured
KW  - iPSC (Other)
KW  - lipid droplet (Other)
KW  - lipid metabolism (Other)
KW  - lipidomics (Other)
KW  - microglia (Other)
KW  - neuroinflammation (Other)
KW  - triglycerides (Other)
KW  - Culture Media (NLM Chemicals)
KW  - Triglycerides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41512865
DO  - DOI:10.1016/j.stemcr.2025.102779
UR  - https://pub.dzne.de/record/285210
ER  -