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. Overall design: Utilizing the IRIS platform, we conducted a comprehensive spatial analysis of molecular profiles and spatial arrangements of cell types in mouse brains. To study the aging-associated transcriptome changes, here we collected brain tissues from adult (4-month) and the aged (23-month) wild-type C57BL/6 mice, with three replicates per age group.