Evidence map›Paper›PMID 41824460›Full record

ArticleCell reports2026

Single-cell epigenomics uncovers heterochromatin instability and transcription factor dysfunction during mouse brain aging.

Maria Luisa Amaral, Sainath Mamde, Michael Miller, Xiaomeng Hou, Jessica Arzavala, Julia Osteen, Nicholas D Johnson, Elizabeth Walker Smoot, Qian Yang, Emily Eisner and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 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

5 · Who and what money

Authors and funding

30 authors.

Maria Luisa AmaralDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
Sainath MamdeDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Michael MillerCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Xiaomeng HouCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jessica ArzavalaComputational Neurobiology 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.
Elizabeth Walker SmootCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Qian YangCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Emily EisnerCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
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.
Cindy Tatiana Báez-BecerraComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jacqueline OlnessCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Joseph Colin KernCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jonathan RinkComputational 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.
Silvia ChoComputational 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.
Nora EmersonComputational 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.
Jackson WillierComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Timothy LoeDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Henry JiaoCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Songpeng ZuDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Quan ZhuCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Sebastian PreisslCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; CIBSS - Centre for Integrative Biological Signaling Studies, University of Freiburg, Freiburg, Germany; Department of Pharmacology and Toxicology, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria; Field of Excellence BioHealth, University of Graz, Graz, Austria.
Allen WangCenter for Epigenomics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
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.
Maria Margarita BehrensComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: mbehrens@salk.edu.
Bing RenDepartment of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; New York Genome Center, New York, NY 10013, USA; Departments of Genetics and Development, Biochemistry and Molecular Biophysics, and Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: bren@nygenome.org.

Funding

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
NIA NIH HHS R01 AG066018
6 · The paper itself

Abstract

The mechanisms regulating transcriptional changes during brain aging remain poorly understood. Here, we use single-cell epigenomics to profile chromatin accessibility and gene expression across eight mouse brain regions at 2, 9, and 18 months of age. In addition to a marked decline in progenitor populations involved in neurogenesis and myelination, we observe widespread and concordant age-associated changes in transcription and chromatin accessibility across both neuronal and glial cell types. These alterations are accompanied by dysregulation of master transcription factors and a shift toward stress-response programs driven by activator protein 1 (AP-1), indicating progressive drift in cellular identity with aging. We further identify region- and cell-type-specific heterochromatin loss, characterized by increased accessibility at H3K9me3-marked domains, activation of transposable elements, and upregulation of long noncoding RNAs, particularly in glutamatergic neurons. Together, these findings reveal age-related disruption of heterochromatin maintenance and transcriptional regulation, highlighting vulnerable brain regions, cell types, and molecular pathways in brain aging.

Indexed as

AgingBrainEpigenomicsHeterochromatinSingle-Cell AnalysisTranscription FactorsAnimalsMaleMiceMice, Inbred C57BLNeuronsHeterochromatinTranscription FactorsagingCP: genomicsCP: neuroscienceepigenomeheterochromatinmouse brainsingle-celltransposable elements

Identifiers

PMID41824460
PMCPMC13189690

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.