Evidence map›Paper›PMID 40475496›Full record

ArticlebioRxiv : the preprint server for biology2025

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 19 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Maria Luisa AmaralDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Sainath MamdeDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Michael MillerCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Xiaomeng HouCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Jessica ArzavalaComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Julia OsteenComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Nicholas D JohnsonComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Elizabeth Walker SmootCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Qian YangCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Emily EisnerCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Qiurui ZengGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Cindy Tatiana Báez-BecerraComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Jacqueline OlnessCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Joseph Colin KernCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Jonathan RinkComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Ariana BarcomaComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Silvia ChoComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Stella CaoComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Nora EmersonComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Jasper LeeComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Jackson WillierComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Timothy LoeDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Henry JiaoCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Songpeng ZuDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Quan ZhuCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Allen WangCenter for Epigenomics, University of California, San Diego, School of Medicine, La Jolla, CA, USA.
Joseph R EckerGenomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Maria Margarita BehrensComputational Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
Bing RenDepartment of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.

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 in brain aging remain poorly understood. Here, we use single-cell epigenomics to profile chromatin accessibility and gene expression across eight brain regions in the mouse brain at 2, 9, and 18 months of age. In addition to a significant decline in progenitor cell populations involved in neurogenesis and myelination, we observed widespread and concordant changes of transcription and chromatin accessibility during aging in glial and neuronal cell types. These alterations are accompanied by dysregulation of master transcription factors and a shift toward stress-responsive programs driven by AP-1, indicating a progressive loss of cell identity with aging. We also identify region- and cell-type-specific heterochromatin decay, characterized by increased accessibility at H3K9me3-marked domains, activation of transposable elements, and upregulation of long non-coding RNAs, particularly in glutamatergic neurons. Together, these results reveal age-related disruption of heterochromatin maintenance and transcriptional programs, identify vulnerable brain regions and cell types, and pinpoint key molecular pathways altered in brain aging.

Identifiers

PMID40475496
PMCPMC12139859

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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.