TY - JOUR
T1 - Evolution of the lipidome uncovers early changes in adrenoleukodystrophy human cortical and spinal organoids
AU - Ferrer, Roberto Montoro
AU - Jaspers, Yorrick R.J.
AU - Coveña, Nicki
AU - Breeuwsma, Nicole
AU - Dijkstra, Inge M.E.
AU - Kempff, Julia
AU - Klinken, Jan Bert van
AU - Wortel, Joke
AU - van Weering, Jan R.T.
AU - Engelen, Marc
AU - Kemp, Stephan
AU - Heine, Vivi M.
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2026/1/16
Y1 - 2026/1/16
N2 - 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.
AB - 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.
KW - Developmental neuroscience
KW - Lipidomics
KW - Nervous system anatomy
UR - https://www.scopus.com/pages/publications/105025151491
UR - https://www.scopus.com/inward/citedby.url?scp=105025151491&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2025.114339
DO - 10.1016/j.isci.2025.114339
M3 - Article
AN - SCOPUS:105025151491
SN - 2589-0042
VL - 29
SP - 1-14, e1-e5
JO - iScience
JF - iScience
IS - 1
M1 - 114339
ER -