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Hypergeometric test with different cell types

Hello,

I have to select the background for a hypergeometric test that I have to perform. The problem is as follow:

I have a list of genes differentially expressed in cell B between "control vs Knock Out" experiment. I want to see if there is an overlap (and via hypergeometric test that is not just by chance) between the genes down-regulated in the Knock out cell B with genes that are Up regulated in cell B between cell A vs cell B. As you can notice the cell B is different from cell A and I am wondering if there is a suitable strategy to handle this problem to perform the hypergeometric test.

Basically, the treatment in experiment B is the knock out of a protein of interest and I would like to know if genes that are downregulated in B (because of the removal of the protein) are also involved in the transition between state A and state B (i assume that genes up-regulated in B in A vs B are involved in the differentiation from cell A to B). We are trying to understand if this protein is promoting the transition between the two states...

Thanks in advance for any suggestion

rna-seq r background selection hypergeometric

This is a case where GSEA would be better than a simply hypergeometric test.

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