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High-throughput single-cell Hi-C (dscHi-C) reveals 3D genome changes during mouse brain aging. These structural alterations impact neuronal and glial cell functions, offering insights into brain development and disease.

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Area of Science:

  • Genomics
  • Neuroscience
  • Cell Biology

Background:

  • Single-cell 3D genome techniques are crucial for understanding tissue complexity.
  • Existing methods have limitations in cell throughput, hindering large-scale studies.

Purpose of the Study:

  • Introduce a high-throughput single-cell Hi-C (dscHi-C) and multi-omics (dscHi-C-multiome) approach.
  • Investigate chromatin structural dynamics during mouse brain aging.
  • Explore the relationship between 3D genome organization and gene expression.

Main Methods:

  • Developed droplet microfluidics-based dscHi-C and dscHi-C-multiome.
  • Profiled 32,777 single cells across three developmental stages (3, 12, 23 months).
  • Analyzed chromatin structural changes and gene expression patterns.

Main Results:

  • Identified significant 3D genome structural changes in aging mouse brains.
  • Genes with structural changes are linked to neuronal metabolism/morphology and glial immune response.
  • Precisely identified cell types and linked genome architecture to gene expression using dscHi-C-multiome.

Conclusions:

  • dscHi-C and dscHi-C-multiome are sensitive, high-throughput tools for studying 3D genome organization.
  • 3D genome structure plays a role in physiological brain aging.
  • These methods are valuable for large-scale cell atlas projects in development and disease.