Spatial Mapping of Mouse Brain Aging through Indexed Sequencing

Here, we have developed a novel methodology called IRIS (Imaging Reconstruction using Indexed Sequencing) that enables cost-effective spatial transcriptomics profiling without relying on optical imaging. Through neighborhood interaction-based reconstruction, IRIS allows extensive analysis of large tissue sections and many replicates with adjustable mapping resolution at only a fraction of the cost of other commercial platforms. With the IRIS platform, we reconstructed a large area spatial area with two whole mouse brain coronal sections. Moreover, we also created a spatially resolved transcriptome atlas of the mouse brain and identified aging-associated changes in gene expression and spatial organization across various brain cell types. Further analysis of cell-cell interaction changes identified aging-associated foci in white matter regions enriched with inflammatory subtypes of microglia and oligodendrocytes. Overall, the IRIS methodology cost-effective and ease-of-use approach makes it broadly applicable to the studies of spatial gene expression changes in various systems.