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Synapse
March 16, 2026Cell Reports1 citationsOpen Access

Single-nucleus multiome analysis in the human prefrontal cortex identifies gene expression and cis-regulatory elements associated with aging

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ACAdam CatchingCWCory A. WellerFHFangle Hu

Key Points

  • This research aims to uncover the molecular changes associated with aging in the human prefrontal cortex.
  • Conducted single-nucleus multiome ATAC plus gene expression profiling.
  • Analyzed 357 human brain samples from individuals aged 15 to 100.
  • Classified cells into seven major types based on canonical marker genes.
  • Correlated open chromatin regions with transcription factor expression to map regulatory networks.
  • Identified cis-regulatory elements linked to gene expression changes.
  • Generated paired transcriptomic and epigenomic profiles for over 1.5 million cells.
  • Cataloged putative cis-regulatory elements associated with aging across cell types.
  • Revealed insights into transcriptional regulation influenced by aging and disease.

Abstract

Summary Aging is an unavoidable part of life, but gaps still remain in the understanding of age-associated molecular changes within the brain. We generated single-nucleus multiome ATAC plus gene expression profiles in 357 human brain samples from European and African admixed ancestry individuals ranging from 15 to 100 years old. The final dataset consisted of paired transcriptomic and epigenomic profiles for over 1.5 million cells. These were classified into seven major cell types using canonical marker genes, and each type was analyzed for features associated with aging. Open chromatin regions were correlated with transcription factor expression to identify age-associated regulatory networks, and co-accessibility identified linked peaks and genes, revealing a catalog of putative cis-regulatory elements by cell type. These multiomic data serve as a resource to characterize transcriptional regulation by cell type and generate hypotheses about how these distinct profiles both influence and are influenced by aging and disease.

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Cite This Study

Catching et al. (2026) studied this question.

synapsesocial.com/papers/69b79e398166e15b153ab33dhttps://doi.org/10.1016/j.celrep.2026.117110
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