Neuroscience Showcase

Build A More Accurate and Complete Molecular Atlas with MERSCOPE™

Accurately characterizing every individual cell within the brain is challenging due to the low expression of many functionally important genes. MERSCOPE’s high detection efficiency, sensitivity and single molecule resolution allow users to build a more accurate and complete molecular atlas.

MERFISH Mouse Brain Receptor Map

To demonstrate the power of MERSCOPE, we generated the MERFISH Mouse Brain Receptor Map that includes canonical cell type markers, nonsensory G-Protein coupled receptors (GPCRs), and Receptor Tyrosine Kinases (RTKs). We designed this specific gene panel because nonsensory GPCRs mediate signaling and may play vital roles behind brain ageing and neurodegenerative disorders. However, GPCRs are notoriously difficult to analyze. Thus, the ability to completely spatially profile GPCR expression across the brain with cellular context can assist with gaining a deeper understanding of brain tissue structure and function.

Overview:

Species
Mouse
Tissue Type
Brain
Gene Panel Size
483
Types of Genes
Canonical cell type markers, GPCRs, RTKs
Number of Samples
9 full slices across 3 positions
Number Biological Replicates
3 per position
Total Transcripts Detected
554,802,908
Total Cells
734,696
Data Output
  • List of all detected transcripts and their spatial locations in three dimensions (CSV)
  • The DAPI and Poly T mosaic images (TIFF)
  • Output from the cell segmentation analysis: the transcripts per cell matrix (CSV), the cell metadata (CSV) and the cell boundaries (HDF5)
Figure 1: MERFISH measurements performed with MERSCOPE on nine mouse brain slices across three positions with three replicates per position.

Insights Gained from MERSCOPE Data

Detect 70X More Transcripts

MERSCOPE detected 70x more transcripts per gene than an array-based platform for a more accurate map of the cellular organization of our selected mouse brain receptors:

Figure 2: A comparison of total RNA detected between the Vizgen MERSCOPE and an array based spatial transcriptomics platform shows that MERSCOPETM detects 70 times more transcripts from mouse brain tissue samples.

Detect Lowly Expressing Genes

Our experiment successfully detected multiple lowly expressed GPCRs including Oxtr, Tshr, and Insr that could be missed by other spatial transcriptomic platforms.

MERSCOPE is capable of a high 100nm resolution that enables us to see where RNA transcripts are located not only within a large 1cm2 tissue section, but inside each single cell.

Figure 3: MERSCOPE can image a large 1cm2 area and provide the location of RNA transcripts within a tissue slice down to the subcellular level with 100nm resolution.

Map Gene Expression by Cell Type

MERSCOPE’s high sensitivity allows us to map gene expression by cell type, as well as see the variation in the gene expression pattern of receptors within the mouse brain.

Figure 4: The variation in the gene expression pattern of eight different receptors between neuronal and non-neuronal cell types and their positions within the mouse brain are detectable by MERSCOPE.

Highly Reproducible MERFISH Measurements

MERSCOPE generates highly reproducible measurements between brain slice replicates, resulting in high confidence in the data.  

Figure 5: Correlation plots between the MERFISH measurements taken with MERSCOPE and bulk RNA-seq show that data generated by MERSOPE is highly quantitative and reproducible across large brain tissue area.

Our MERFISH Mouse Receptor Map demonstrates that MERSCOPE is a leading tool for building a superior molecular atlas because it produces true spatial transcriptomic data for whole tissues slices down to the subcellular level. MERSCOPE enables researchers to harness the power of MERFISH technology and gain greater insights into brain cell function.
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