{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:06:14Z","timestamp":1792073174160,"version":"4.4.0"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008731","name":"Association Europ\u00e9enne contre les Leucodystrophies","doi-asserted-by":"publisher","award":["2019\u2010020C2"],"award-info":[{"award-number":["2019\u2010020C2"]}],"id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016062","name":"Stichting Metakids","doi-asserted-by":"publisher","award":["2023\u2010102"],"award-info":[{"award-number":["2023\u2010102"]}],"id":[{"id":"10.13039\/100016062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["016.196.310"],"award-info":[{"award-number":["016.196.310"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>X\u2010linked adrenoleukodystrophy (ALD) is a peroxisomal disorder resulting from pathogenic variants in the <jats:italic>ABCD1<\/jats:italic> gene that primarily affects the nervous system and is characterized by progressive axonal degeneration in the spinal cord and peripheral nerves and leukodystrophy. Dysfunction of peroxisomal very long\u2010chain fatty acid (VLCFA) degradation has been implicated in ALD pathology, but the impact on astrocytes, which critically support neuronal function, remains poorly understood. Fibroblasts from four ALD patients were reprogrammed to generate human\u2010induced pluripotent stem cells (hiPSC). hiPSC\u2010derived astrocytes were generated to study the impact of ALD on astrocytic fatty acid homeostasis. Our study reveals significant changes in the lipidome of ALD hiPSC\u2010derived astrocytes, characterized by an enrichment of VLCFAs across multiple lipid classes, including triacylglycerols, cholesteryl esters, and phosphatidylcholines. Importantly, ALD hiPSC\u2010derived astrocytes not only exhibit intrinsic lipid dysregulation but also affect the dendritic tree complexity of neurons in co\u2010culture systems. These findings highlight the cell\u2010autonomous effects of pathogenic variants in the ABCD1 protein on astrocytes and their microenvironment, shed light on potential mechanisms underlying ALD neuropathology, and underscore the critical role of astrocytes in neuronal health.<\/jats:p>","DOI":"10.1002\/jimd.12832","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T08:38:38Z","timestamp":1734683918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Altered lipid profile and reduced neuronal support in <scp>human induced pluripotent stem cell<\/scp>\u2010derived astrocytes from adrenoleukodystrophy patients"],"prefix":"10.1002","volume":"48","author":[{"given":"Roberto Montoro","family":"Ferrer","sequence":"first","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC, Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Complex Trait Genetics Centre for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorrick R. J.","family":"Jaspers","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M. E.","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Breeuwsma","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescence Psychiatry Emma Children's Hospital, Amsterdam UMC Location, Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Bert","family":"van Klinken","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam  Amsterdam The Netherlands"},{"name":"Core Facility Metabolomics Amsterdam UMC Location, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cato","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Complex Trait Genetics Centre for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Child and Adolescence Psychiatry Emma Children's Hospital, Amsterdam UMC Location, Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Engelen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Emma Children's Hospital, Amsterdam UMC, Amsterdam Leukodystrophy Center, Amsterdam Neuroscience, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2023-064X","authenticated-orcid":false,"given":"Stephan","family":"Kemp","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivi M.","family":"Heine","sequence":"additional","affiliation":[{"name":"Department of Complex Trait Genetics Centre for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Child and Adolescence Psychiatry Emma Children's Hospital, Amsterdam UMC Location, Vrije Universiteit Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11020283"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/361726a0"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.90"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2010.11.010"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201374"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856\u2010024\u201000605\u20109"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000257129.51273.73"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2018.09.036"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531\u20108249(199901)45:1<100::aid\u2010rt16>3.0.co;2\u2010u"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.07.007"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00051.2021"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2023.100364"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109861(91)90303\u2010z"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.08.022"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105050"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102722"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241612912"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102782"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.03.006"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/472459"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.001"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010023\u201000756\u20104"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.128"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002605"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23120"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.11.019"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25585"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7626"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101302"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154597"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20106937\u20101_5"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010021\u201001105\u20107"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2018.08.017"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010018\u20100085\u2010z"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u201000783\u20104"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010019\u201002926\u2010x"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010022\u201001180\u20109"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5504.657"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010199211000\u201000007"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010024\u201003105\u20100"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.09.015"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142500"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.26502\/jbb.2642\u201091280091"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00742"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23978"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR\u2010D\u201023\u201001470"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108572"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz4564"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44140-3"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.06.003"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118182"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101655\u20109"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt186"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90028-J"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21391"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113195"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003960\u2010y"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12832","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:08:40Z","timestamp":1754906920000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/jimd.12832"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12832","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]},"assertion":[{"value":"2024-09-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12832"}}