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Array Tomography Workflow for the Targeted Acquisition of Volume Information using Scanning Electron Microscopy

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Transcriptome tomography for brain analysis in the web-accessible anatomical space.

Yuko Okamura-Oho¹, Kazuro Shimokawa, Satoko Takemoto

¹Advanced Computational Sciences Department, Advanced Science Institute (ASI), RIKEN, Saitama, Japan. yoho@brent-research.org

|October 3, 2012

Summary

We developed Transcriptome Tomography, a novel method for mapping gene expression in 3D. This technique enables comprehensive visualization of gene activity within anatomical structures, aiding in understanding complex biological functions and diseases.

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Area of Science:

Genomics
Neuroscience
Bioinformatics

Background:

Understanding gene expression-anatomy associations is vital for deciphering complex mammalian genome functions.
Current methods lack comprehensive 3D mapping capabilities for endogenous gene expression.

Purpose of the Study:

To introduce Transcriptome Tomography, a novel technique for comprehensive 3D mapping of gene expression.
To create a web-accessible standard space for gene expression data.

Main Methods:

Conjugation of sequential tissue-block sectioning with block-face imaging for 3D reconstruction.
Serial sectioning in three orthogonal planes and tomographic mapping of gene expression densities.
Generation of 36,000 whole mouse brain expression maps from microarray data of 61 fractions.

Main Results:

Successfully generated a comprehensive 3D gene expression dataset for the entire mouse brain (ViBrism).
Validated mapping accuracy against existing data for expression location and density.
Demonstrated disease-related gene expression patterns for Huntington's disease and Bdnf.

Conclusions:

Transcriptome Tomography provides a rapid, unbiased method for creating 3D gene expression maps.
The technique is applicable to various biological molecules and sample types (tissues, organs, embryos).
This framework facilitates research using open standards for molecular-based structural understanding and biological/medical insights.