Suppose I have a whole tissue composed of multiple cell types. I homogenize the tissue and use half for an array experiment and the other half I separate using FACs. I would like to demonstrate that each cell type has a unique expression pattern. Rather than comparing every cell type with every other cell type, would it be sound to demonstrate that a given cell differs significantly from the background (the whole tissue expression)?
A useful way of representing the transcriptome relationship between tissues is to run a PCA. Closer related tissues will be displayed closer to each other. We did this with over 50 human and mouse tissues and obtained biologically meaningful representations. See:
Another example is shown here: