{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:28:09Z","timestamp":1768818489184,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NS114775"],"award-info":[{"award-number":["NS114775"]}]},{"name":"National Institute of Health","award":["NS114245"],"award-info":[{"award-number":["NS114245"]}]},{"name":"National Institute of Health","award":["A10263"],"award-info":[{"award-number":["A10263"]}]},{"name":"National Institute of Health","award":["A30973"],"award-info":[{"award-number":["A30973"]}]},{"name":"Henry Ford Hospital","award":["NS114775"],"award-info":[{"award-number":["NS114775"]}]},{"name":"Henry Ford Hospital","award":["NS114245"],"award-info":[{"award-number":["NS114245"]}]},{"name":"Henry Ford Hospital","award":["A10263"],"award-info":[{"award-number":["A10263"]}]},{"name":"Henry Ford Hospital","award":["A30973"],"award-info":[{"award-number":["A30973"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>X-adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder caused by mutations in the ABCD1 gene encoding the peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). Similar mutations in ABCD1 may result in a spectrum of phenotypes in males with slow progressing adrenomyeloneuropathy (AMN) and fatal cerebral adrenoleukodystrophy (cALD) dominating most cases. Mouse models of X-ALD do not capture the phenotype differences and an appropriate model to investigate the mechanism of disease onset and progress remains a critical need. Here, we generated induced pluripotent stem cell (iPSC) lines from skin fibroblasts of two each of apparently healthy control, AMN, and cALD patients with non-integrating mRNA-based reprogramming. iPSC lines expanded normally and expressed pluripotency markers Oct4, SOX2, NANOG, SSEA, and TRA-1\u201360. Expression of markers SOX17, Brachyury, Desmin, OXT2, and beta tubulin III demonstrated the ability of the iPSCs to differentiate into all three germ layers. iPSC-derived lines from CTL, AMN, and cALD male patients were differentiated into astrocytes. Differentiated AMN and cALD astrocytes lacked ABCD1 expression and accumulated saturated very long chain fatty acids (VLCFAs), a hallmark of X-ALD, and demonstrated differential mitochondrial bioenergetics, cytokine gene expression, and differences in STAT3 and AMPK signaling between AMN and cALD astrocytes. These patient astrocytes provide disease-relevant tools to investigate the mechanism of differential neuroinflammatory response in X-ALD and will be valuable cell models for testing new therapeutics.<\/jats:p>","DOI":"10.3390\/ijms26041576","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T05:10:22Z","timestamp":1739423422000},"page":"1576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Generation and Characterization of Human iPSC-Derived Astrocytes with Potential for Modeling X-Linked Adrenoleukodystrophy Phenotypes"],"prefix":"10.3390","volume":"26","author":[{"given":"Navtej","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6563-5424","authenticated-orcid":false,"given":"Jaspreet","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Hospital, Detroit, MI 48202, USA"},{"name":"Department of Physiology, Michigan State University, Lansing, MI 48824, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/ncpneuro0421","article-title":"X-linked adrenoleukodystrophy","volume":"3","author":"Moser","year":"2007","journal-title":"Nat. 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