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Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms.

Overview

Authors: Itsuki Kageyama1,2, Hiroya Yamada1, Mirai Yamazaki1, Takuya Wakasugi1, Yuri Kamiya1, Masaki Ohshiro3, Manaka Ito3, Yoshiki Tsuboi2, Takashi Watanabe4, Genki Mizuno5, Yoshitaka Ando3, Hiroaki Ishikawa3, Koji Suzuki2, Koji Ohashi3, Eiji Munetsuna1,6
ORCID iDs: Hiroya Yamada
  1. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan
  2. Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake, Japan
  3. Department of Informative Clinical Medicine, Fujita Health University School of Medical Sciences, Toyoake, Japan
  4. Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Japan
  5. Department of Medical Technology, Tokyo University of Technology School of Health Sciences, Ota, Japan
  6. Department of Animal Science and Biotechnology, Azabu University School of Veterinary Medicine, Sagamihara, Japan
Institutions: Fujita Health University (Japan); Tokyo University of Technology (Japan); Azabu University (Japan)
Journal: Stem cell reports, volume 21, issue 7, article 102996
Dates: received 19 October 2025; accepted 4 June 2026; published online 2 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.stemcr.2026.102996 · PMID 42392085 · PMCID PMC13385421 · OpenAlex W7167088584
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), rat (organism)
Methods: Statistics, Evoked potentials
Keywords: DOHaD, fructose, osteopontin, DNA methylation, stem cell programming, epigenetics
MeSH: Diet*, Epigenesis, Genetic*, Neural Stem Cells*, Prenatal Exposure Delayed Effects*, Stress, Physiological*, Animals, Developmental Origins of Health and Disease, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, DNA Methyltransferase 3A, Female, Fructose, Hippocampus, Neurogenesis, Osteopontin, Pregnancy, Rats (* major topic)
Topic: Epigenetics and DNA Methylation (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Japan Society for the Promotion of Science
Citations: not cited yet (Europe PMC); 51 references in the paper
Research resources: HRP-Goat anti-mouse RRID:AB_10679675, Rabbit anti-CD11b RRID:AB_1310048, HRP-Goat anti-rabbit RRID:AB_2099233, Mouse anti-OPN RRID:AB_2194997, Rabbit anti-DNMT3A RRID:AB_2277449, Rabbit anti-SOX2 RRID:AB_2341193, Alexa Fluor 488-goat anti-mouse RRID:AB_2534084, Alexa Fluor 594-goat anti-rabbit RRID:AB_2534116, Rabbit anti-NeuN RRID:AB_2744676, Mouse anti-NESTIN RRID:AB_305313, Rabbit anti-GFAP RRID:AB_305808, Rabbit anti-βIII Tubulin (TUJ1) RRID:AB_444319, HRP-Mouse anti-β-actin RRID:AB_867494, Mouse anti-BrdU RRID:AB_95024

Abstract

The developmental origins of health and disease (DOHaD) hypothesis suggests that environmental exposures during development can induce long-term health effects, yet the cellular origin of such persistence remains unclear. Here, we suggest that neural stem cells (NSCs) may develop aberrant properties that persist with possible involvement of epigenetic mechanisms linking maternal dietary stress to neurocognitive impairments. In a rat model of maternal high-fructose corn syrup intake, offspring showed hippocampus-dependent memory deficits and reduced neurogenesis. NSCs from fetal and adolescent hippocampi exhibited persistent dysfunction with transcriptomic dysregulation. Mechanistically, transient downregulation of DNA methyltransferase 3A in fetal NSCs was associated with sustained repression of secreted phosphoprotein 1, encoding intracellular osteopontin (iOPN). iOPN overexpression partially restored NSC function, supporting a potential causal link. Our study proposes a DOHaD framework in which stem cells with lasting alterations may retain epigenetic traces of early life stress, with implications for organ systems and disease risk.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

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

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Data

Datasets cited

Data and code availability

All data reported in this paper will be shared by the lead contact upon request. This study did not generate any unique code. The RNA-seq data analyzed in this paper were obtained from GEO under accession number GSE111172 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111172) (Yagi et al., 2020). The microarray data generated in this study have been deposited in GEO under accession number GSE332845 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332845). Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 6 keywords, 17 MeSH terms, 1 funder, 51 references, 14 RRIDs.

Cite

This paper

Kageyama, I., Yamada, H., Yamazaki, M., Wakasugi, T., Kamiya, Y., Ohshiro, M., Ito, M., Tsuboi, Y., Watanabe, T., Mizuno, G., Ando, Y., Ishikawa, H., Suzuki, K., Ohashi, K., & Munetsuna, E. (2026). Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms. Stem cell reports, 21(7), 102996. https://doi.org/10.1016/j.stemcr.2026.102996

BibTeX

@article{kageyama2026neural,
author = {Kageyama, Itsuki and Yamada, Hiroya and Yamazaki, Mirai and Wakasugi, Takuya and Kamiya, Yuri and Ohshiro, Masaki and Ito, Manaka and Tsuboi, Yoshiki and Watanabe, Takashi and Mizuno, Genki and Ando, Yoshitaka and Ishikawa, Hiroaki and Suzuki, Koji and Ohashi, Koji and Munetsuna, Eiji},
title = {{Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms}},
journal = {Stem cell reports},
year = {2026},
month = jul,
volume = {21},
number = {7},
pages = {102996},
publisher = {Elsevier},
issn = {2213-6711},
doi = {10.1016/j.stemcr.2026.102996},
url = {https://doi.org/10.1016/j.stemcr.2026.102996},
pmid = {42392085},
pmcid = {PMC13385421}
}

RIS

TY - JOUR
AU - Kageyama, Itsuki
AU - Yamada, Hiroya
AU - Yamazaki, Mirai
AU - Wakasugi, Takuya
AU - Kamiya, Yuri
AU - Ohshiro, Masaki
AU - Ito, Manaka
AU - Tsuboi, Yoshiki
AU - Watanabe, Takashi
AU - Mizuno, Genki
AU - Ando, Yoshitaka
AU - Ishikawa, Hiroaki
AU - Suzuki, Koji
AU - Ohashi, Koji
AU - Munetsuna, Eiji
TI - Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms
T2 - Stem cell reports
J2 - Stem Cell Reports
PY - 2026
DA - 2026/07/02
VL - 21
IS - 7
SP - 102996
SN - 2213-6711
PB - Elsevier
DO - 10.1016/j.stemcr.2026.102996
UR - https://doi.org/10.1016/j.stemcr.2026.102996
LA - en
ER -

CSL-JSON

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