Molecular Cartography of the Human and Mouse Down Syndrome Brain [MERFISH]

Given the importance of linking human and model system pathobiology, we also performed highly multiplexed RNA in situ spatial transcriptomics on a well-established trisomic mouse model (Ts65Dn) to study the cellular landscape of the trisomic brain during early life and aging. We profiled the spatial transcriptome of > 240,000 cells in the mouse brain and identified trisomy-associated gene expression patterns in the molecular control of neurogenesis, gliogenesis, and myelination. Multiplexed error-robust fluorescence in situ hybridization (MERFISH) was performed on postnatal day 0 (P0) and 6 month (6mo) euploid and trisomic (Ts65Dn) mice (n=3 per condition). Coronal sections of the entire brain were used for analysis. Min Yi, Feng