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Related Concept Videos

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Related Experiment Video

Updated: Sep 19, 2025

Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
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Single-Cell Epigenomics Uncovers Heterochromatin Instability and Transcription Factor Dysfunction during Mouse Brain

Maria Luisa Amaral1,2, Sainath Mamde1, Michael Miller3

  • 1Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.

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|June 6, 2025
PubMed
Summary

Brain aging involves widespread transcriptional and chromatin changes, leading to cell identity loss. This study reveals disrupted heterochromatin maintenance and identifies vulnerable brain regions and cell types.

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Area of Science:

  • Neuroscience
  • Genomics
  • Aging Research

Background:

  • Mechanisms of transcriptional regulation in brain aging are not well understood.
  • Aging impacts cellular function and gene expression in the brain.

Purpose of the Study:

  • To investigate age-related changes in chromatin accessibility and gene expression across mouse brain regions.
  • To identify molecular pathways and cell types affected by brain aging.

Main Methods:

  • Single-cell epigenomics (chromatin accessibility and gene expression profiling).
  • Analysis across eight mouse brain regions at three different ages (2, 9, and 18 months).

Main Results:

  • Significant decline in neurogenesis and myelination progenitor cells.
  • Widespread, concordant changes in transcription and chromatin accessibility in glial and neuronal cells.
  • Dysregulation of transcription factors, shift to stress-response programs (AP-1), and loss of cell identity.
  • Region- and cell-type-specific heterochromatin decay, including increased accessibility at H3K9me3 domains, transposable element activation, and lncRNA upregulation, especially in glutamatergic neurons.

Conclusions:

  • Brain aging disrupts heterochromatin maintenance and transcriptional programs.
  • Identifies specific vulnerable brain regions and cell types during aging.
  • Pinpoints key molecular pathways, including stress-response and heterochromatin dynamics, altered in brain aging.