Spatial Transcriptomics correlated Electron Microscopy [MERFISH]

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. Brain sections were collected from mice after unilaterally induced demyelination injury and analyzed by MERFISH