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Related Experiment Video

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Mouse Forebrain Region Features and Cholinergic Neurons Subtyping: Integrated Analysis with Spatial Multi-omics.

Yujie Chen1, Mengyao Han2, Jiayue Meng1

  • 1National Genomics Data Center & Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.

Genomics, Proteomics & Bioinformatics
|November 20, 2025
PubMed
Summary

This study reveals low correlation but high functional similarity between mRNA and protein expression in the forebrain. We identified novel cholinergic neuron (CN) subtypes and genes in the striatum and basal forebrain using advanced spatial analysis.

Keywords:
Cholinergic neurons-celltypingMouse forebrain regionMulti-omicsRCA-FISHSpatial transcriptome-proteome

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Area of Science:

  • Neuroscience
  • Genomics
  • Proteomics

Background:

  • Forebrain regions exhibit unique gene expression patterns that are not fully understood.
  • Cholinergic neurons (CNs) are crucial for sensory and motor regulation in the forebrain.
  • Understanding the relationship between mRNA and protein expression is key to deciphering neuronal function.

Purpose of the Study:

  • To analyze region-specific feature genes in forebrain and Isocortex subregions at transcriptomic and proteomic levels.
  • To investigate the correlation and functional similarity between mRNA and protein expression.
  • To identify novel feature genes specific to cholinergic neurons (CNs) and their subtypes in the striatum and basal forebrain.

Main Methods:

  • Transcriptomic and proteomic analysis of forebrain and Isocortex subregions.
  • Spatial-transcriptome and immunofluorescence joint analysis (STIF) to overcome resolution limitations.
  • Validation of spatial distribution and expression patterns using external datasets and rolling circle amplification fluorescence in situ hybridization (RCA-FISH).

Main Results:

  • A low correlation but high functional similarity was observed between mRNA and protein expression.
  • Identification of CNs and CN-subtypes specific feature genes in the striatum and basal forebrain.
  • Spatial distribution and expression patterns of identified genes were validated, confirming their specificity.

Conclusions:

  • The study provides new insights into the relationship between mRNA and protein expression in neuronal pathways.
  • Novel feature genes contributing to the heterogeneity and functional diversity of cholinergic neurons were identified.
  • The findings enhance our understanding of cholinergic neuron subtypes and their roles in forebrain regulation.