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APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells.

Overview

Authors: Wiebke Schulten1, Nele Johanne Czaniera1,2, Mehran Fazel1, Barbara Kaltschmidt2,3, Christian Kaltschmidt1,2
  1. Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany; (W.S.); (N.J.C.); (M.F.); (C.K.)
  2. Forschungsverbund BioMedizin Bielefeld, Ostwestfalen-Lippe (OWL) (FBMB E.V.), 33617 Bielefeld, Germany
  3. Molecular Neurobiology, University of Bielefeld, 33615 Bielefeld, Germany
Institutions: Bielefeld University (Germany)
Journal: International journal of molecular sciences, volume 27, issue 10, article 4325
Dates: received 25 March 2026; accepted 6 May 2026; published online 12 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3390/ijms27104325 · PMID 42196306 · PMCID PMC13207287 · OpenAlex W7161027471
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Smoothing, state filtering, decompositions
Keywords: Alzheimer’s disease, iPSCs, APOE4, RNA sequencing, neurodevelopment, differentiation, EGR, TNFR, metallothionein
MeSH: Apolipoprotein E4*, Induced Pluripotent Stem Cells*, Inflammation*, Signal Transduction*, Transcription, Genetic*, Alzheimer Disease, Apolipoprotein E3, Cell Differentiation, Gene Expression Regulation, Genotype, Humans, Protein Interaction Maps, SOXB1 Transcription Factors (* major topic)
Topic: Pluripotent Stem Cells Research (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 69 references in the paper

Abstract

The APOE4 allele represents the strongest genetic risk factor for late-onset Alzheimer’s 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–protein 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data Availability Statement

The original data presented in the study are openly available in GitLab at https://gitlab.com/fazel.mehran96/rna_seq_alzheimer (accessed on 20 March 2026).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 9 keywords, 13 MeSH terms, 69 references.

Cite

This paper

Schulten, W., Czaniera, N. J., Fazel, M., Kaltschmidt, B., & Kaltschmidt, C. (2026). APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells. International journal of molecular sciences, 27(10), 4325. https://doi.org/10.3390/ijms27104325

BibTeX

@article{schulten2026apoe4,
author = {Schulten, Wiebke and Czaniera, Nele Johanne and Fazel, Mehran and Kaltschmidt, Barbara and Kaltschmidt, Christian},
title = {{APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells}},
journal = {International journal of molecular sciences},
year = {2026},
month = may,
volume = {27},
number = {10},
pages = {4325},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
issn = {1422-0067},
doi = {10.3390/ijms27104325},
url = {https://doi.org/10.3390/ijms27104325},
pmid = {42196306},
pmcid = {PMC13207287}
}

RIS

TY - JOUR
AU - Schulten, Wiebke
AU - Czaniera, Nele Johanne
AU - Fazel, Mehran
AU - Kaltschmidt, Barbara
AU - Kaltschmidt, Christian
TI - APOE4 Alters Early Transcriptional Programs and Inflammatory Signaling in Human Induced Pluripotent Stem Cells
T2 - International journal of molecular sciences
J2 - Int J Mol Sci
PY - 2026
DA - 2026/05/12
VL - 27
IS - 10
SP - 4325
SN - 1422-0067
PB - Multidisciplinary Digital Publishing Institute (MDPI)
DO - 10.3390/ijms27104325
UR - https://doi.org/10.3390/ijms27104325
LA - en
ER -

CSL-JSON

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