A new technique, dubbed intron seqFISH enables scientists to image 10,421 genes at once within individual cells. 

The technique is a major advance in being able to identify what’s going on across the genome in hundreds of different cells at once. 

Imaging Over 10,000 Genes at Once Within Individual Cells

3D Construction: 982 transcription active sites, corresponding to individual genes, are present in this cell.(Credit: Cai Laboratory)

Previously, researchers could only image four to five genes at the time in cells with microscopy. Scaling seqFISH up to a genomic level, now enables the imaging of over 10,000 genes — about half of the total number of genes in mammals — within single cells. 

A paper describing the research is published in Cell. 

In order for genetic instructions to be turned into an actual functioning protein, a process called transcription must first occur. This process often occurs in pulses, or “bursts”. 

First, a gene will be read and copied into a precursor messenger RNA, or pre-mRNA, like jotting a quick, rough draft. This molecule then matures into messenger RNA, or mRNA, akin to editing the rough draft. During the “editing” process, certain regions called introns are cut out of the pre-mRNA. 

The research team chose to focus on labelling introns because they are produced so early in the transcription process, giving a picture of what a cell is doing at the precise moment of gene expression.

Using the intron seqFISH technique, each nitron is labelled with a unique fluorescent barcode, enabling it to be seen with a microscope. 

Seeing introns reveals which genes are currently turned on in individual cells, how strongly they are expressed, and where they are located. 

10,421 introns — and therefore, 10,421 genes — can be imaged at once. 

Because introns stay where the gene is physically located, fluorescently imaging introns allows researchers to visualize where genes are located within the chromosome, the large structure that DNA folds into within the cell’s nucleus. In this work, the team was surprised to discover that most active, protein-encoding genes are located on the surface of the chromosome, not buried inside of it.

“This technique can be applied to any tissue,” said Caltech Research Professor in Biology, Long Cai, who is a collaborator on the Human Cell Atlas. 

“Intron seqFISH can help identify cell types and also what the cells are going to do, in addition to giving us a look at the chromosome structure in the same cells.” 


Materials provided by California Institute of Technology. Note: Content may be edited for style and length.