Fig. 4. Spatiotemporal changes in cell composition and function during colon aging.

(a,b) Analysis approach. cSplotch is used to characterize variability in cell-type specific gene expression across age and region (a), followed by MCP analysis with DIALOGUE⁵⁴ (b) on inferred profiles for abundant cell types (e.g., cell types A and B) in each MROI across ages and regions. MCPs are returned as sets of genes with high correlation between two or more cell types across conditions (with positively (+, up) and negatively (−, down) contributing genes from each cell type (Methods). (c,d) Aging-associated MCPs. (c) Activity score (y axis) of selected MCPs (panels) from different MROIs (top left label) in each time point (x axis) and region (labels on top). Gray area: aging window. (d) Scaled (dot size) and absolute (dot color) change in log expression ($\bar{\beta }$) relative to 12 weeks of each gene (rows) in each time point (columns) for selected up (+) and down (−) regulated genes from the MCPs in (c), sorted by their associated cell type (label on right).