Leading the Global Expansion of Spatial Transcriptomics
Spatial transcriptomics is the combination of high-resolution single-cell sequencing and three-dimensional imaging. With this additional spatial context, researchers can now understand not only individual cell behavior, but also the interaction of neighboring cells and communication pathways across an entire tissue. For a more in-depth look at spatial transcriptomics, check out our recent blog article on the subject.
2015 to 2020
The MERFISH technology behind Vizgen’s MERSCOPE® Platform began development almost a decade ago at Harvard University in the lab of Xiaowei Zhuang, PhD, alongside Jeffrey Moffitt, PhD, (serving on Vizgen’s Scientific and Technical Advisory Board), and Vizgen co-founders George Emanuel, PhD, and Jiang He, PhD.
Between 2015 and 2018, Dr. Zhuang’s lab published six papers detailing the development of MERFISH technology in leading journals such as Science and Nature Methods. The first of which, published in Science in 2015 titled “Spatially resolved, highly multiplexed RNA profiling in single cells,” introduced the scientific world to MERFISH as a tool to simultaneously image 100 to 1,000 RNA species at the single-cell level. The paper has had a massive impact on the field and has been cited in over 1,000 per-reviewed publications.
RNA imaging techniques – such as single-molecule fluorescence in situ hybridization (smFISH) – were widely used tools for quantifying RNA at this time. However, the exponential increase in detection errors limited the number of RNA species that could be sequentially imaged, making it challenging to perform the larger-scale transcriptomic analyses required to characterize single cells in spatial context.
Dr. Zhuang’s team developed a novel combinatorial barcoding scheme where each targeted transcript is assigned a unique binary barcode, generated by sequential rounds of imaging. This dramatically increases multiplexing capacity while maintaining accuracy and consistency of the data.
FIGURE 1: MERFISH’s error-correcting barcoding scheme and combinatorial labeling ensure the highest detection accuracy of transcripts. If the background fluorescence does cause a readout error, the system can easily assign the readout to the nearest correct barcode. MERFISH experiments don’t require sequencing.
Back then, Dr. Zhuang and colleagues already recognized the incredible potential of this nascent technology, concluding in the final paragraph of the paper:
“Given its ability to quantify RNAs…without amplification bias while preserving native context, we envision that MERFISH will enable many applications of in situ transcriptomic analyses of individual cells in culture or complex tissues.”
Chen KH et al. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science. 2015 Apr 24;348(6233). PMID: 25858977
2020 to 2022
Fast forward five years to 2020 when spatially resolved transcriptomics was named “Method of the Year” by Nature, and Dr. Zhuang’s research group published six more papers demonstrating the use of MERFISH in multiple applications, including sub-cellular RNA profiling and characterization of individual neurons in the brain motor cortex.
FIGURE 2: MERFISH enables scientists to spatially localize transcripts with nanometer-scale resolution, mapping gene expression across whole tissues and discovering the complex arrangement of cell types and states.
In January 2022, Vizgen launched MERSCOPE in the US as the first ever single-cell, high-plex spatial genomics platform in the world. Powered by MERFISH technology, it provides the highest detection efficiency and resolution available for spatially profiling the transcriptome, from whole tissue sections to single-cell and even sub-cellular imaging.
FIGURE 3: The MERSCOPE® Platform launched in the US at the start of 2022. MERSCOPE combines MERFISH technology with high resolution imaging, fluidics, image processing, and automation to deliver a complete end-to-end spatial genomics solution. MERFISH measurements taken with MERSCOPE correlate with bulk RNA-seq data and are highly reproducible between replicates. MERSCOPE provides a greater detection efficiency than array-based platforms, identifying 70x more transcripts per gene.
In October 2022, Vizgen announced the availability of MERSCOPE to Asia-Pacific (APAC), Europe, Middle East, and Africa (EMEA) markets. With the hiring of two sales and marketing leaders in these areas (Dr. Mickael Ploquin as Regional Director for EMEA, and Paul Rasmussen as Commercial Leader for APAC and Japan), and plans for the near future to expand into additional markets including India, MERSCOPE is solidifying its reputation for unmatched sensitivity, specificity, and biological accuracy across the world.
Today, MERFISH technology has been used to generate data for nearly 100 papers – both in peer-reviewed journals or available as preprints – across the fields of neuroscience, oncology, and immunology. As the field of spatial genomics grows and researchers discover its many potential uses, Vizgen is leading the charge to make the technology available to the global scientific community.
FIGURE 4: Spatial distribution of RNA transcripts in colon cancer. 417 genes were spatially profiled across human colon cancer tumor sections. Image shows the expression of a subset of 10 RNA species including THBS1 (dark green), FBLN1 (pink), SDC4 (gray), GIPHBP1 (magenta), DERL3 (dark yellow), FABP (light yellow)1, IGHA1 (bright red), KRTS6 (dark blue), SOX9 (light blue), SPP1 (lime green). Scale bar is 1mm.
Vizgen has prioritized the release of publicly available datasets, knowing that to build this new field, researchers need access to the technology. This data not only shows off the impressive capabilities of the MERSCOPE® Platform, but also gives new scientists readily access to the tools they need to incorporate spatial analysis into their research. Currently, Vizgen’s data release program comprises the world’s largest single-cell spatial genomics public dataset and includes 26 samples, over 10 million cells, and nearly 6 billion transcripts, spanning multiple cancers, liver and the brain, in both mice and humans.
FIGURE 5: The MERSCOPE FFPE Human Immuno-oncology Data Release was generated using the MERSCOPE FFPE Sample Prep Solution. The data release includes 16 MERFISH datasets generated by the MERSCOPE® Platform from 8 different human tumor types, each measuring 500 genes representing approximately 4 billion transcripts and 9 million cells cumulatively.
After the initial launch of MERSCOPE at the beginning of 2022, Vizgen released new reagents to expand the capabilities of the platform and MERFISH experiments. The MERSCOPE Protein Stain Kits enable researchers to detect transcripts and protein markers simultaneously within the same tissue. The MERSCOPE FFPE Sample Prep Solution allows scientists to spatially analyze formalin fixed paraffin embedded (FFPE) tissues, which represent a large portion of preserved cancer tissue samples. Tiling protein co-staining with MERFISH spatial transcriptomics on MERSCOPE provides researchers with a way to generate true high-quality spatial multiomic datasets featuring single-cell gene expression and morphological information.
FIGURE 6: A. Immunofluorescence staining of cytokeratin proteins in fresh frozen human uterus cancer tissue with mouse pan-Cytokeratin antibody. B and C. MERSCOPE co-detection of transcripts from a panel of 244 genes and cytokeratin proteins using MERSOPE protein stain kit and pan-cytokeratin antibody in fresh frozen human uterus cancer tissue. B. Visualization of detected proteins. C. Visualization of detected transcripts and proteins demonstrating multiomic measurements by the MERSCOPE® Platform, enabling researchers to better understand cell interactions, signaling, and overall tissue behavior.
2023 and Beyond
This year, Vizgen continues to lead the way in spatial transcriptomics by launching the first predesigned gene panels for the MERSCOPE® Platform. Vizgen’s new PanCancer Pathways (Human) and PanNeuro Cell Type (Mouse) Panels provide researchers with curated lists of genes focused on oncology and neuroscience research, making MERFISH experiments even easier for labs around the world.
FIGURE 7: MERSCOPE Predesigned Gene Panels. The MERSCOPE PanCancer Pathways Panel features a robust list of curated genes targeting canonical signaling pathways of cancer for spatially characterizing tumor behavior at cellular and subcellular levels. The MERSCOPE PanNeuro Cell Type Panel features a curated list of genes built to identify all major cell types and established neuron subtypes in the mouse brain with MERFISH.
This is a tremendously exciting time of growth for Vizgen as we continue our mission to pave the way for the global expansion of the spatial transcriptomics field. The scientific community is beginning to realize the potential of this technology and Vizgen, together with its world-class team of partners, is achieving the goal of positioning MERSCOPE as a truly global platform available to researchers all over the world.