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EVOLUTION OF THE LIPIDOME UNCOVERS EARLY CHANGES IN ADRENOLEUKODYSTROPHY HUMAN CORTICAL AND SPINAL ORGANOIDS

ABSTRACT:

Lipids are critical for the structure, signaling, and metabolism of the central nervous system (CNS), yet their roles during human brain development remain underexplored due to limited tissue availability. X-linked adrenoleukodystrophy (ALD), a peroxisomal disorder caused by ABCD1 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.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive, Liquid Chromatography MS - negative, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12973 | MetaboLights | 2025-11-17

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12973_LC-MS_negative__metabolite_profiling.txt	Txt
	a_MTBLS12973_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12973_LC-MS_positive__metabolite_profiling.txt	Txt
	a_MTBLS12973_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt

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