High-Resolution Spatial Transcriptomics at Lower Cost

A group of scientists from Prof. Stein Aerts's lab at VIB-KU Leuven present Nova-ST, a novel spatial transcriptomics method that could revolutionize tissue sample gene expression profiling.

Large-scale, high-resolution spatial tissue analysis will become more widely available and reasonably priced using Nova-ST, which will be extremely beneficial to researchers. The study was published in Cell Reports.

The study of gene expression in a single cell or a population of cells is known as transcriptomics; however, it typically lacks spatial information regarding the locations of the active genes. This obstacle hindered the comprehension of intricate biological processes that depend on particular patterns of gene activity in tissues.

Spatial transcriptomics has become a potent tool that enables researchers to map gene expression throughout a tissue section in its spatial context. Nevertheless, the methods currently in use frequently have compatibility problems, high costs, or poor resolution.

Prof. Stein Aerts's lab, the VIB.AI Single-Cell Microfluidics and Bioinformatics expertise units, and the VIB-KU Leuven Center for Brain & Disease Research have developed a novel open-source spatial transcriptomics workflow called Nova-ST. With its creative methodology, Nova-ST surpasses these constraints and provides increased affordability, remarkable resolution, and adaptability.

Under the Hood

The innovative modification of the Illumina NovaSeq 6000 S4 or the new generation Novaseq X sequencing flow cells, which are frequently utilized for large-scale DNA sequencing, forms the basis of Nova-ST. The densely nanopatterned surface of these flow cells is covered in tiny, randomly barcoded nanowells that are arranged in a hexagonal lattice.

Each well serves as a capture site for mRNA molecules from a particular location within the tissue sample. Thanks to this densely nanopatterned surface, Nova-ST can achieve high spatial resolution, which may be able to capture the footprint of individual cells.

We then use these capture sites to snag mRNA molecules while preserving their spatial coordinates. Sequencing these captured mRNA molecules reveals the gene expression profile for each capture site. By piecing together this information, we can reconstruct a detailed map of gene activity across the entire tissue section.”

Dr. Suresh Poovathingal, Experimental Development and Optimization Lead, Vlaams Instituut voor Biotechnologie

Advantages

The new platform has several significant benefits. First of all, it is affordable. Several Nova-ST chips can be produced from a single flow cell by utilizing widely accessible Illumina flow cells and a unique chip-cutting method, which drastically lowers costs in comparison to current approaches. Second, Nova-ST's densely nanopatterned surface enables high spatial resolution, which may enable the detection of single-cell gene expression.

Thirdly, Nova-ST can be used with different kinds of tissue, making it an adaptable instrument for researching various biological systems. Furthermore, the fact that Nova-ST is compatible with the upcoming Illumina flow cells implies that the company can gain from developments in sequencing technology.

Importantly, Nova-ST’s open-source nature makes the protocol accessible to a wider range of researchers and allows for further customization. Our workflow is designed to be user-friendly and adaptable, ensuring that researchers can tailor the technique to their specific needs.”

Dr. Kristofer Davie, Data Analysis Lead, Vlaams Instituut voor Biotechnologie

Impact

The development of Nova-ST is part of a larger effort by the spatial transcriptomics research community to democratize access and create platforms that further a variety of biomedical research areas. These efforts include the development of the recently published Open-ST platform by scientists at the Max Delbrück Center in Germany and the evolution of Seq-Scope and its recent variations at the University of Michigan.

Stein Aerts' lab is already using Nova-ST and the expertise units to further their colleagues' neurodegeneration and cancer biology research. For instance, they prepared muscle samples for research on the impact of neurodegenerative illnesses on neuromuscular junctions by the Sandrine Da Cruz lab (VIB-KU Leuven). Furthermore, they are collaborating to expand the Nova-ST platform with the Diether Lambrechts lab (VIB-KU Leuven).

This expansion will make it possible to study the distribution of immune cells in tumors receiving immunotherapy by enabling the simultaneous spatial analysis of immune cell receptors and gene expression. These partnerships demonstrate the useful applications of Nova-ST and its potential to have an impact on a variety of fields.

Prof. Stein Aerts emphasized, “Nova-ST is a game-changer for research across multiple fields, from cancer biology to plant biology. By making this platform open source, we aim to empower scientists worldwide to explore and innovate.”