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Evolution of the lipidome uncovers early changes in adrenoleukodystrophy human cortical and spinal organoids

2025/12/04 by Roberto Montoro Ferrer, Yorrick Jaspers, Nicki Coveña +9 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Peroxisome Proliferator-Activated Receptors #Cholesterol and Lipid Metabolism #Adipose Tissue and Metabolism

paper · doi:10.1016/j.isci.2025.114339

openalex publication_date 2025/12/04 · openalex created_date 2025/12/04 · openalex updated_date 2026/07/23

Abstract

mutations, disrupts very long-chain fatty acid (VLCFA) degradation, leading to axonal degeneration and demyelination. To investigate lipid dynamics in CNS development and ALD pathogenesis, we generated human induced pluripotent stem cell (hiPSC)-derived cortical and spinal cord organoids and performed lipidomics over 200 days. Lipidomic analysis revealed a dynamic lipidome, with changes in lipid abundance, saturation, and chain length reflecting neurodevelopment. ALD hiPSC-derived organoids exhibited significant lipid alterations over time, including elevated VLCFA levels and reductions in brain-relevant lipids, such as sulfatides and gangliosides, in cortical organoids. These findings provide a foundational resource for studying lipid dynamics in CNS development and emphasize the value of organoids for understanding ALD and other CNS diseases.

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