New Study in Nature Highlights Use of Vizgen’s MERSCOPE and MERFISH

The Neurodevelopment of Down Syndrome − New Study in Nature Highlights Use of Vizgen’s MERSCOPE and MERFISH

Neuroscientists at SickKids Research Institute in Toronto, Canada, conducted landmark research that uncovered new insights into the neurodevelopment and molecular mechanisms of Down syndrome, one of the most common genetic causes of intellectual disability. The spatial transcriptomics described in this study was enabled by Vizgen’s MERSCOPE® Platform and MERFISH™ chemistry. The new study is available in the Nature paper entitled: “Molecular cartography of the human Down syndrome and trisomic mouse brain.”

This study delves extensively into the complex multicellular processes underlying Down syndrome neurodevelopment. The outcome of the research is a significant step toward filling a gap in the biological understanding of how the trisomy in Down syndrome causes patient symptoms. The researchers show how the disruption of specific neurodevelopmental processes leads to a developmental abnormality of the cerebral cortex, the brain’s outermost layer.

Down syndrome, which can be identified during pregnancy by prenatal screening, is the most common chromosomal condition diagnosed in the United States. Each year, on average, nearly 6,000 babies born in the United States have Down syndrome, which is, in simple terms, a genetic condition in which a person is born with an extra chromosome, affecting how the brain and body develop.

The research team performed spatial transcriptomics, single-nucleus sequencing and proteomics on mid-gestational prenatal human cortex. The findings suggest that these issues may impact the formation and function of critically important nerve and support cells.

The researchers also performed highly multiplexed RNA in situ spatial transcriptomics on a well-established trisomic mouse model to study the cellular landscape of the trisomic brain during early development and maturation. They profiled the spatial transcriptome of more than 240,000 cells in the mouse brain and, as noted in the study, identified trisomy-associated gene expression patterns in the molecular control of neurogenesis and gliogenesis. 

This research is a landmark study about the molecular mechanisms of chromosomal abnormality in Down syndrome. It has the potential to significantly advance the biomedical community’s understanding of this genetic disorder. 

Interestingly, to build upon its human data, the research team reported that they used the Ts65Dn mouse model of Down syndrome, a widely used system for investigating potential therapeutics and mechanisms. As the study explains, they performed imaging-based spatial transcriptomics (multiplexed error-robust fluorescence in situ hybridization; MERFISH) in the Ts65Dn mouse model: postnatal day 0 and 6 months.

MERFISH provides the highest detection efficiency available for spatially profiling gene expression across whole tissues and resolving individual transcripts with nanometer-scale resolution through combinatorial labeling, sequential imaging, and error-robust barcoding.

As a trusted partner with researchers around the world, Vizgen is advancing neuroscience research with spatial multi-omics solutions, enabling researchers to obtain deeper insights than previously possible. Both MERSCOPE and MERFISH play an important role in studies of disease. 

Well known as the industry’s first commercially available high-plex single-cell spatial genomics platform, the MERSCOPE platform has given researchers the ability to access the spatial dimension to answer new kinds of scientific questions and make significant biological discoveries. The MERSCOPE platform has been effective as a tool for researchers to explore the molecular mechanisms of a number of diseases on a spatial transcriptome-wide level. 

Vizgen has continued to enhance both technologies to give researchers even more capabilities. The MERSCOPE Ultra platform, a leading high-plex, spatial genomics solution, enables researchers to unlock new insights by mapping and quantifying RNA species in tissues at single-cell resolution. MERSCOPE Ultra offers two flow cell sizes, which enable cost efficiency and flexible experimental setups. The larger flow chamber expands the imageable area to 3.0 cm², efficiently accommodating larger and multiple smaller samples.

Now available for both the MERSCOPE Ultra and the MERSCOPE Platform, MERFISH 2.0, which was launched earlier this year, leverages enhanced RNA anchoring and signal enhancement to build on the original MERFISH sensitivity and reproducibility. With MERFISH 2.0, researchers are able to directly map and quantify the spatial distribution of RNA species in individual cells in a wider array of samples. 

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