Project description:Current spatial transcriptomics methods provide molecular and spatial information but no morphological readout. Here, we present STEM - a method that correlates multiplexed error-robust FISH with electron microscopy from neighboring tissue sections of the same sample. STEM links transcriptional and spatial organization of single cells with ultrastructural morphology of the tissue in vivo. Using STEM to characterize demyelinated white-matter lesions allowed us to link morphology of myelin-laden foamy microglia to transcriptional signature. Moreover, we revealed that interferon-response microglia have unique morphology and are enriched near CD8 T-cells.
Project description:Current spatial transcriptomics methods identify cell types and states in a spatial context but lack morphological information. Electron microscopy, in contrast, provides structural details at nanometer resolution without decoding the diverse cellular states and identity. STEM address this limitation by correlating multiplexed error-robust FISH with electron microscopy from adjacent tissue sections. Using STEM to characterize demyelinated lesions in mice, we were able to bridge spatially resolved transcriptional data with morphological information on cell identities. This approach allowed us to link the morphology of foamy microglia and interferon-response microglia with their transcriptional signatures.
Project description:Spatially resolved transcriptomic profiling of somatostatin-positive (Sst+) interneurons in the postnatal mouse brain using MERFISH (MERSCOPE, Vizgen). Two coronal brain sections corresponding to Paxinos Atlas levels 125 and 133 were collected from P5 C57BL/6J mice to characterize Sst+ cell type diversity and spatial organization
Project description:The extracellular matrix (ECM) and basement membrane (BM) are critical structural and signaling components of the human pancreatic endocrine niche. To define the cellular sources and spatial organization of vascular ECM programs in the adult human pancreas, we performed MERFISH spatial transcriptomics on FFPE pancreatic tissue sections from non-diabetic (ND) and type 2 diabetic (T2D) donors using the Vizgen MERSCOPE platform with a custom 300-gene panel enriched for extracellular matrix, vascular, endocrine, and stromal-associated genes.
Project description:We optimized a workflow combining imaging-based spatial transcriptomics (MERFISH) and immunostaining on ganglion cell layer retinal flatmounts of C57/Bl6J mice.The MERFISH data shows molecularly-defined retinal ganglion cell types types exhibited non-uniform distributions. We also analyzed local neighborhoods for each cell and registered several RGC types as enriched in the perivascular niche.