The human body accommodates greater than 30 trillion cells. Until recently, the sheer variety of cells within the organism meant that approaches to understanding human diseases and developmental processes based on the evaluation of single cells were a futuristic vision. The event of recent sequencing methods is currently revolutionizing our understanding of cellular heterogeneity. These technologies can detect rare and even latest cell types by extracting and sequencing the genetic information from the cells based on ribonucleic acid chains.

In cooperation with Helmholtz Munich, Professor Matthias Meier from the Centre for Biotechnology and Biomedicine at Leipzig University and his research group have developed a latest, effective and relatively inexpensive method to make rare cell types, cell communication types and disease patterns visible in tissue. The researchers have now published their findings in the distinguished journal “Nature Communications”.

All methods of single-cell evaluation require cells to be detached from the tissue composite, losing spatial details about cell types and thus information concerning the cellular environment, cellular communication pathways or function. To acquire spatially resolved details about individual cells, imaging and sequencing techniques have to be used together. Lately, several approaches have been developed to unify the merging of imaging and sequencing data. Depending on the research query, different parameters similar to spatial resolution, detection limit, accessibility of the ribonucleic acids and value were weighed against one another. An earlier evaluation method was based on the concept of attaching local information to the ribonucleic acids using a barcode based on the sequence of DNA bases. After extraction of all of the ribonucleic acids and subsequent mass sequencing, the barcodes will be used to create a synthetic image.

That is where Johannes Wirth’s work got here in. As a doctoral researcher in Matthias Meier’s lab, the researcher at Helmholtz Munich has developed a complicated workflow that makes it possible to accumulate locally resolved genomic data paired with high-quality microscopy images. This permits the visualization of rare cell types, cell communication types and disease patterns in tissue. The main target was on the event of a latest microfluidic chip that makes it possible to research ribonucleic acid chains in large tissue sections at low price. “In comparison with the unique method, the brand new approach has increased the quantity of image information per pixel by an element of six or twelve. Which means that we will resolve about 5000 genes per pixel, which allows us to visualise rare cell types within the kidney or liver,” explains Wirth. By comparison, an ordinary HD screen can only display the three primary colours with 256 different brightness levels per pixel.

Along with the technical advances, the team also provided an open source evaluation pipeline to make the tactic easily accessible. As the tactic is suitable for a wide selection of tissues, it’s going to facilitate studies of complex diseases and multi-organ functions and dysfunctions.

The tactic we have now developed, which mixes imaging and sequencing techniques, was a vision until recently. It has revolutionized our understanding of cellular heterogeneity and allowed us to search out latest cell types in all organisms.”

Professor Matthias Meier, Centre for Biotechnology and Biomedicine, Leipzig University

With the event of single-cell sequencing methods, it’s now possible to higher understand cellular developmental pathways and the way diseases progress.

Source:

Journal reference:

Wirth, J., et al. (2023). Spatial transcriptomics using multiplexed deterministic barcoding in tissue. Nature Communications. doi.org/10.1038/s41467-023-37111-w.