Original title: New DNA microscope draws a 3D map of life "from the inside out".

Scientists at the University of Chicago in the United States have developed a revolutionary imaging technique called volumetric DNA microscopy. The technology allows for a 3D map of life "from the inside out", allowing scientists to build a 0D map of complex genetic material by labeling and tracking interactions between molecules, providing unprecedented insight into living organisms. The findings were published in the new issue of Nature Biotechnology.

Although traditional gene sequencing methods can reveal the rich genetic information in a sample, they cannot show the specific location of a specific gene sequence in the sample, or its relationship with surrounding genes and molecules. To compensate for this shortcoming, newly developed technology can capture the identity of genetic material and record its location at the same time. This is achieved by adding short DNA sequence tags, known as unique molecular identifier (UMI), to individual DNA or RNA molecules, and then tracking the interactions between these tags. This interaction helps to create a molecular network that reflects the spatial arrangement of genes, resulting in a three-dimensional image.

When using a volumetric DNA microscope, the UMI attaches to the DNA and RNA molecules inside the cell and begins to replicate. This process generates a unique event identifier UEI. Each UEI is unique, and they help determine the specific location of each gene molecule. Adjacent UMI interactions also generate more UEIs, which provides the computational model with the information needed to reconstruct the original position and create a spatial map of gene expression.

Unlike traditional microscopes, which rely on light or lenses, volumetric DNA microscopy relies on calculating the interactions between molecules to create images. This method has been likened to using cell phone data to determine the location of people in a city, just as knowing cell phone numbers can help locate individuals, and analyzing interactions between molecules can also infer their location in the body.

This technique does not rely on prior knowledge and is therefore suitable for exploring gene expression in unknown contexts. For example, in cancer research, it can be used to map the interaction between the tumor microenvironment and the immune system, which is of great significance for the development of more precise cancer immunotherapy or customized personalized vaccines. (Zhang Mengran)