Evidence map›Paper›PMID 41819104›Full record

ArticleCell2026

Cell-type-specific transposon demethylation and TAD remodeling in aging mouse brain.

Qiurui Zeng, Wenliang Wang, Wei Tian, Amit Klein, Anna Bartlett, Hanqing Liu, Joseph R Nery, Rosa G Castanon, Julia Osteen, Nicholas D Johnson and 24 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
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

34 authors.

Qiurui ZengGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Wenliang WangGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Wei TianGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Amit KleinGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Anna BartlettGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Hanqing LiuGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Junior Fellow, Faculty of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA.
Joseph R NeryGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Rosa G CastanonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Julia OsteenComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Nicholas D JohnsonComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Wubin DingGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Huaming ChenGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jordan AltshulGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mia KenworthyGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cynthia ValadonGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
William OwensGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Zhanghao WuSky Computing Lab, University of California, Berkeley, Berkeley, CA 94709, USA.
Maria Luisa AmaralBioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Nathan R ZemkeDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA; Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.
Yuru SongNeurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA.
Cindy Tatiana Báez-BecerraComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Silvia ChoComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Chumo ChenGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jackson WillierComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Stella CaoComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jonathan RinkComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jasper LeeComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Ariana BarcomaComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jessica ArzavalaComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Nora EmersonComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Yuancheng Ryan LuWhitehead Institute for Biomedical Research, Cambridge, MA 02138, USA.
Bing RenDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA; New York Genome Center, 101 Avenue of the Americas, New York, NY 10013, USA; Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 701 W 168th Street, New York, NY 10032, USA.
M Margarita BehrensComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: mbehrens@salk.edu.
Joseph R EckerGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: ecker@salk.edu.

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Alan Saghatelian · 1985 to 2026
$82.8M
Molecular SignaturesU19MH114831 · NIMH · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI CALLAWAY, EDWARD M, ECKER, JOSEPH R · 2017 to 2021
$24.6M
Epigenome-based Cell Census and Regulatory Element Discovery in the Aging Mouse BrainR01AG066018 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ECKER, JOSEPH R, REN, BING · 2019 to 2023
$4.6M
Spectral Configured Bigfoot Sorter for Salk Institute Flow Cytometry CoreS10OD034268 · OD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI O'CONNOR, CAROLYN PEY-MIN · 2023 to 2023
$724k
BD FACSAria Fusion for Flow Cytometry Core FacilityS10OD023689 · OD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ZHENG, YE · 2018 to 2018
$530k
Systematic Identification and Mechanistic Characterization of Novel Oxidative Protective Genes to Prevent RPE DegenerationK99EY037340 · NEI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Yuancheng Lu · 2025 to 2026
$346k
NCI NIH HHS P30 CA014195NEI NIH HHS K99 EY037340NIA NIH HHS R01 AG066018NIH HHS S10 OD023689NIH HHS S10 OD034268NIMH NIH HHS U19 MH114831
6 · The paper itself

Abstract

Aging is a major risk factor for neurodegenerative diseases, yet the underlying epigenetic mechanisms remain unclear. Here, we generated a comprehensive single-nucleus cell atlas of brain aging across multiple brain regions, comprising 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei. Integration with companion transcriptomic and chromatin accessibility data yielded a cross-modality taxonomy of 36 major cell types. We observed that transposable element (TE) methylation alone distinguished age groups, showing cell-type-specific genome-wide demethylation. Chromatin conformation analysis demonstrated age-related increases in topologically associated domain (TAD) boundary strength with enhanced accessibility at CCCTC-binding factor (CTCF) binding sites. Spatial transcriptomics across 895,296 cells revealed regional heterogeneity during aging within identical cell types. Finally, we developed deep-learning models that reliably predict age-related gene expression changes using multi-modal epigenetic features, providing mechanistic insights into gene regulation. Age-related comparisons use a 2-month baseline reflecting the late-adolescent/early-young adult stage. This dataset advances our understanding of brain aging and offers potential translational applications.

Indexed as

AgingBrainDNA Transposable ElementsAnimalsCCCTC-Binding FactorChromatinDNA MethylationEpigenesis, GeneticMaleMiceMice, Inbred C57BLTranscriptomeCCCTC-Binding FactorChromatinDNA Transposable Elements3D genomebrain agingdeep learningDNA methylationmulti-omicneurons and gliassingle-cellspatial transcriptometopologically associating domainstransposable elements

Identifiers

PMID41819104
PMCPMC13007725

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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.