Extended Data Fig. 9: Histological, transcriptional, and lipid changes in Sandhoff disease brains.
From: Microglia–neuron crosstalk through Hex–GM2–MGL2 maintains brain homeostasis
A) Quantification of IBA1+ microglia in postmortem brain tissue of Sandhoff disease patients and unaffected controls. Orange indicates Sandhoff disease, blue unaffected controls. Th: thalamus, Cwm: Cerebellum – white matter, Cgm: Cerebellum – grey matter, Ctx: cortex, WM: subcortical white matter. Each bar represents one patient. B) Immuohistochemistry for phagocytic and lysosomal markers: KIM1P, p22phox, lysozyme, and LAMP2. C) H&E staining thalamic sections of Sandhoff disease patients and healthy controls. D) H&E stains depicting cellular ganglioside deposition and an enlarged hypercellular perivascular space. E) Bielschowsky (Biel) stain highlighting the axonal network. F) Immunostaining for axonal- and neurofilament-associated proteins: SMI31 (phosphorylated neurofilaments), SMI35 (non-phosphorylated neurofilaments), and SMI312 (pan-axonalhighly phosphorlylated neurofilaments marker). Note the abnormal accumulation of SMI31 in perikarya of degenerationg neurons with ganglioside accumulation as well as axonal swellings. G) Heat map featuring the top cell-type-specific marker genes across the different cell types. H) Marimekko charts depicting the proportions of each cell type or cluster separated by disease condition. I) Feature Plots depicting cluster defining genes. J) MALDI MSI of cortex and thalamus from Sandhoff disease patients and unaffected controls. Ion images show spatial distribution of gangliosides; color scale indicates intensity (arbitrary units). K) Volcano plot indicating the differentially regulated lipids between Sandhoff disease patients and unaffected controls measured by untargeted lipidomics (liquid chromatography mass spectrometry (LC-MS)). Two-tailed Welch’s t-test was used for statistical testing.
