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Updated: Jan 13, 2026
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by
Aiko Toda Robert1, Amanda McQuade2, Sascha J Koppes-den Hertog1
1Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU Amsterdam, Amsterdam, the Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, the Netherlands.
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.
Insights
Human microglia-like cells (iMGL) generated via different methods show distinct lipid profiles. Supplementing induced transcription factor (iTF) iMGL with B-27 or L-carnitine normalizes lipid metabolism and promotes a homeostatic state.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Microglial lipid metabolism is crucial in Alzheimer's disease (AD) and aging.
- Human induced pluripotent stem cell-derived microglia-like cells (iMGL) are valuable tools for studying microglial function in vitro.
- Existing iMGL generation protocols, such as embryoid body-based and induced transcription factor (iTF)-dependent methods, may yield cells with different characteristics.
Purpose of the Study:
- To compare the lipidomes of iMGL generated by different protocols.
- To investigate the impact of differentiation methods on microglial lipid metabolism.
- To identify factors influencing iMGL lipid profiles and their implications for AD research.
Main Methods:
- Comparative lipidomics analysis of iMGL derived from embryoid body-based and iTF-dependent methods.
- Quantification of various lipid classes, with a focus on triglycerides (TGs).
- Assessment of the effects of B-27 supplement and L-carnitine on iMGL lipid profiles and function.
Main Results:
- Significant differences in lipid profiles, particularly triglycerides (TGs), were observed between iMGL from different protocols.
- TGs were markedly increased in iTF-derived iMGL, linked to the absence of B-27 supplement.
- Supplementation with B-27 or L-carnitine reduced TGs in iTF iMGL, restoring a homeostatic state and metabolic responsiveness.
Conclusions:
- iMGL differentiation methods substantially influence microglial lipidomes.
- The B-27 supplement, or L-carnitine, plays a critical role in regulating lipid metabolism in iTF-derived iMGL.
- These findings highlight the importance of considering differentiation protocols when studying lipid-associated neuroinflammation and AD in iMGL models.
