Cell Atlas of the Mouse Brain
with high, 100nm-resolution images of the nucleus, total mRNA stains, and single-cell segmentation results (Figure 1). Vizgen’s MERFISH Mouse Brain Receptor Map is the
Figure 1: Vizgen’s MERFISH Mouse Brain Receptor Map was generated using a gene panel of 483 genes. It identifies 734,696 cells and pinpoints the precise location of 554,802,908 RNA transcripts. Together, the map offers an unprecedented look into the molecular basis of the murine brain.
positions of 554,802,908 RNA transcripts from 483 genes within 734,696 cells. And not only does the dataset provide information about gene expression, it also provides the exact position of each detected transcript within the sample, along
largest dataset of single-cell spatial transcriptomics available to the public to date and is free for researchers who wish to explore new ways to analyze extremely high-volume data and to gain a direct window into the cellular, subcellular, and functional organization of an intact brain and beyond. Tis dataset allows direct visualization of the expression profile of hundreds of genes across the entire brain slice and also within individual cells, down to subcellular resolution of approximately 100nm. It also enables traditional single-cell analysis researchers to surpass standard lower-resolution techniques to characterize and map individual cells based on each cell’s gene expression profile. In addition to capturing information about highly expressed genes that provide a reference, MERFISH’s high sensitivity and detection efficiency enabled a major victory: the dataset captures information about hundreds of genes, such as nonsensory g-protein coupled receptors (GPCRs), that are expressed at such low levels within the tissue that they had been previously difficult to characterize (Figure 2). Notably, the Mouse Brain Receptor Map contains a gold mine of data on medically relevant species such as the OXTR (oxytocin receptor) [9], TSHR (thyroid stimulating hormone receptor) [10], and INSR (insulin receptor) [11]. With its wealth of phenotypic data in a spatial context, the dataset is charged with insight into how these rare species accomplish their roles within the body.
Bringing GPCRs out of the Shadows GPCRs make up the largest fam-
Figure 2: MERFISH high detection efficiency and resolution. The images represent a comparison between a MERFISH measurement on a MERSCOPE instrument and a measurement from an oligo array capture- based technology in the left column, highlighting the expression of opioid receptor delta 1 (OPRD1) in the right column. MERSCOPE consistently detects ∼70-fold more copies of each transcript.
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ily of transmembrane signaling mol- ecules—about 1% of the human genome—and help regulate virtually all physiological processes in our bod- ies [4,12]. Tey are estimated to be the targets of approximately 34 percent of all FDA-approved drugs on the market [13]. GPCRs have incredible relevance to human health, but several roadblocks make in vivo molecular analysis diffi- cult. Namely, they tend to be expressed in very low levels in cells, there is a lack of antibodies to detect them, and they have conserved structural proper- ties not amenable to experimentation. However, it is known that GPCRs come in two flavors: sensory and nonsensory. Sensory GPCRs receive input from the external environment. On the other hand, there are an estimated 370 species of nonsensory GPCRs, all expressed in the brain. Ninety percent of these are involved
in development, neuronal
www.microscopy-today.com • 2021 November
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