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Spatial dynamics of brain development and neuroinflammation.

Di Zhang1, Leslie A Rubio Rodríguez-Kirby2, Yingxin Lin3

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

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Summary

This study maps mouse brain development and neuroinflammation using spatial tri-omic sequencing. It reveals shared and distinct molecular mechanisms underlying brain development and disease.

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Area of Science:

  • Neuroscience
  • Genomics
  • Developmental Biology

Background:

  • Understanding brain development and neuroinflammation requires mapping molecular changes across space and time.
  • Spatial multi-omics approaches offer unprecedented resolution for studying complex biological systems like the brain.

Purpose of the Study:

  • To create a spatiotemporal tri-omic atlas of the developing mouse brain.
  • To investigate molecular mechanisms of brain development and neuroinflammation.
  • To compare developmental processes in mouse and human brains.

Main Methods:

  • Spatial tri-omic sequencing (spatial ATAC-RNA-protein sequencing and spatial CUT&Tag-RNA-protein sequencing).
  • Multiplexed immunofluorescence imaging (co-detection by indexing (CODEX)).
  • Generation of a spatiotemporal atlas from postnatal day 0 (P0) to P21 in mice.

Main Results:

  • Identified temporal persistence and spatial spreading of chromatin accessibility for layer-defining transcription factors in the cortex.
  • Observed dynamic chromatin priming of myelin genes in the corpus callosum and a role for projection neurons in axonogenesis and myelination.
  • Detected shared molecular programs between development and neuroinflammation, with microglia showing conserved and distinct inflammatory/resolution programs.

Conclusions:

  • Brain development and neuroinflammation share common and differential molecular mechanisms.
  • Spatial multi-omics provides a powerful resource for studying brain function and disease.
  • The study offers insights into coordinated axonogenesis and myelination during development.