ArticleGlia2026
C9orf72 Repeat Expansion Induces Metabolic Dysfunction in Human iPSC-Derived Microglia and Modulates Glial-Neuronal Crosstalk.
Article in Glia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
5 citing papers in PubMed.
- C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression.Stem cell reports · 2026Article
- Microglia in C9orf72-associated amyotrophic lateral sclerosis: More or less active?Neural regeneration research · 2026Article
- Review
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- Article
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Authors and funding
13 authors.
Funding
Abstract
The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type-specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)-derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single-cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC-derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia-driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.