Evidence map›Paper›PMID 40461639›Full record

ArticleThe EMBO journal2025

Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation.

Shuzo Matsubara, Kanae Matsuda-Ito, Haruka Sekiryu, Hiroyoshi Doi, Takumi Nakagawa, Naoya Murao, Hisanobu Oda, Kinichi Nakashima, Taito Matsuda

Abstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shuzo Matsubara *Stem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Kanae Matsuda-ItoStem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Haruka SekiryuStem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Hiroyoshi DoiStem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.ORCID http://orcid.org/0000-0002-8910-2980
Takumi NakagawaStem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Naoya MuraoLaboratory of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, Miyazaki, 889-1601, Japan.ORCID http://orcid.org/0009-0006-8531-1730
Hisanobu OdaDivision of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, Kumamoto, 861-4193, Japan.
Kinichi NakashimaStem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. nakashima.kinichi.718@m.kyushu-u.ac.jp.ORCID http://orcid.org/0000-0001-5901-9628
Taito Matsuda *Stem Cell Biology and Medicine, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. matsuda.taito@naist.ac.jp.ORCID http://orcid.org/0000-0002-9859-5967

Funding

AMED JP20gm1310008 and JP24wm0625306JST971 FOREST Program JPMJFR231ZMEXT | Japan Society for the Promotion of Science (JSPS) JP16H06527MEXT | Japan Society for the Promotion of Science (JSPS) JP18K14820MEXT | Japan Society for the Promotion of Science (JSPS) JP20J20975MEXT | Japan Society for the Promotion of Science (JSPS) JP21H02808MEXT | Japan Society for the Promotion of Science (JSPS) JP23K18451
6 · The paper itself

Abstract

Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional regulation that compromises hippocampal NSC activity during the early stage of chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on NSCs and newly generated neurons across different stages. Integrated data analysis revealed continuous alterations in the chromatin profile of hippocampal NSCs and their progeny from neonatal to mature adult stages, accompanied by consistent changes in transcriptional profiles. Further, decreased expression of Setd8, encoding the enzyme for histone H4 monomethylation at lysine 20 (H4K20me1), underlies age-related changes in mouse hippocampal NSCs. Notably, depletion of Setd8 elicits alterations in gene expression and epigenetic regulation that phenocopy age-related changes, and impairs NSC activity, leading to hippocampal memory deficits. Together, our study provides a global map of longitudinal chromatin and transcriptome changes during brain aging and identifies mechanistic insights into early-onset decline of NSC activity and hippocampal neurogenesis that precedes functional aging.

Indexed as

AgingCellular SenescenceEpigenesis, GeneticHippocampusHistone-Lysine N-MethyltransferaseNeural Stem CellsAnimalsDown-RegulationMiceMice, Inbred C57BLNeurogenesisHistone-Lysine N-MethyltransferaseAgingEpigeneticsHippocampusNeural Stem Cell

Identifiers

PMID40461639
PMCPMC12218407

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.