{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:07:27Z","timestamp":1779253647500,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The APOE4 allele represents the strongest genetic risk factor for late-onset Alzheimer\u2019s disease (AD), yet its influence on early cellular programs remains poorly understood. In this study, we investigated transcriptional differences between human induced pluripotent stem cells (iPSCs) carrying the APOE3 or APOE4 genotype. RNA sequencing revealed pronounced genotype-dependent transcriptional changes, with enrichment of genes associated with neural development and metallothioneins in APOE4 cells, while genes related to extracellular matrix organization and cell adhesion were downregulated. Protein\u2013protein interaction network analysis confirmed the presence of clusters linked to neurodevelopmental processes and cellular stress responses in APOE4 cells. Increased expression and nuclear localization of the early neural marker SOX1 further suggest a shift towards early neural lineage commitment in APOE4 cells. In addition, altered expression of early growth response (EGR) transcription factors and reduced TNFR2 protein levels indicated genotype-specific differences in stress and inflammatory signaling pathways. Together, these findings suggest that APOE genotype-dependent alterations in transcriptional regulation, stress responses, and inflammatory signaling may already emerge in pluripotent cells and potentially influence early differentiation programs.<\/jats:p>","DOI":"10.3390\/ijms27104325","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:44:26Z","timestamp":1778658266000},"page":"4325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Wiebke","family":"Schulten","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nele Johanne","family":"Czaniera","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany"},{"name":"Forschungsverbund BioMedizin Bielefeld, Ostwestfalen-Lippe (OWL) (FBMB E.V.), 33617 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehran","family":"Fazel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"Forschungsverbund BioMedizin Bielefeld, Ostwestfalen-Lippe (OWL) (FBMB E.V.), 33617 Bielefeld, Germany"},{"name":"Molecular Neurobiology, University of Bielefeld, 33615 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kaltschmidt","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany"},{"name":"Forschungsverbund BioMedizin Bielefeld, Ostwestfalen-Lippe (OWL) (FBMB E.V.), 33617 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s13287-024-04065-9","article-title":"Comparative Analysis of Regulations and Studies on Stem Cell Therapies: Focusing on Induced Pluripotent Stem Cell (iPSC)-Based Treatments","volume":"15","author":"Song","year":"2024","journal-title":"Stem Cell Res. 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