Spatial transcriptomics

Spatial Transcriptomics Overview

MERFISH Diagram

Spatial transcriptomics ii

Spatial transcriptomics is a groundbreaking technique in molecular biology that allows researchers to measure gene expression within the spatial context of a tissue. This method combines traditional histology with high-throughput sequencing technologies to provide a comprehensive view of the transcriptome in situ.

Overview

Spatial transcriptomics enables the mapping of gene activity to specific locations within a tissue section. This is achieved by capturing mRNA from tissue sections and sequencing it while preserving the spatial information. The resulting data can be used to create detailed maps of gene expression, which can be correlated with histological features.

Methodology

The process of spatial transcriptomics typically involves several key steps:

1. Tissue Preparation: A tissue sample is collected and sectioned. The sections are then placed on a specialized slide that contains spatially barcoded oligonucleotides.
2. mRNA Capture: The tissue sections are permeabilized to allow mRNA to bind to the barcoded oligonucleotides.
3. cDNA Synthesis and Sequencing: The captured mRNA is reverse transcribed into cDNA, which is then sequenced. The spatial barcodes are used to map the sequencing reads back to their original locations in the tissue.
4. Data Analysis: The sequencing data is analyzed to generate spatial maps of gene expression. This involves aligning the reads to a reference genome and quantifying gene expression levels.

Applications

Spatial transcriptomics has a wide range of applications in biological research and medicine:

• Cancer Research: It can be used to study the tumor microenvironment and identify spatial patterns of gene expression that are associated with different cancer subtypes.
• Neuroscience: Researchers can map gene expression in the brain to understand the molecular basis of neural circuits and brain function.
• Developmental Biology: It allows for the study of gene expression dynamics during embryonic development.
• Pathology: Spatial transcriptomics can be used to identify molecular signatures of diseases in tissue samples, aiding in diagnosis and treatment planning.

Advantages and Limitations

Advantages

• High Resolution: Provides detailed spatial information that is not available with bulk RNA sequencing.
• Comprehensive: Allows for the simultaneous analysis of thousands of genes.
• In Situ Analysis: Preserves the spatial context of gene expression, which is crucial for understanding tissue architecture and function.

Limitations

• Technical Complexity: The method requires specialized equipment and expertise.
• Cost: High-throughput sequencing and the preparation of spatially barcoded slides can be expensive.
• Data Analysis: The large amount of data generated requires sophisticated computational tools and resources for analysis.

Related Techniques

• Single-cell RNA sequencing
• In situ hybridization
• Laser capture microdissection
• Immunohistochemistry

See Also

• Transcriptomics
• Genomics
• Proteomics
• Bioinformatics