Fig. 3: Atf4 and the unfolded protein response pathway are activated in deeply quiescent chief cells.

a Gene Ontology (GO) term enrichment analyses (biological process) of the GFP⁺ chief cells. The p-values and gene counts of top ten GO terms enriched in GFP⁺ cells in comparison to Epcam⁺ cells are shown. The top three terms were shown in blue characters. The p value of each GO term is color-labeled. b A gene concept network for the GO terms enriched in GFP⁺ cells. Blue dots represent the top three terms shown in a (1, protein folding: 2, response to unfolded protein: 3, chaperone cofactor-dependent protein refolding). Genes that were associated with these terms were shown. Genes belonging to Atf4 regulon (Atf3, Chac1) are shown in red. Extent of induction of these genes in GFP⁺ cells are shown as color shading. c The top ten transcription factors that were differentially activated between GFP⁺ and Epcam⁺ cells. VIPER activation scores of each transcription factor in GFP⁺ and Epcam⁺ cells are color-coded. d Upregulation of the indicated Atf4 regulon genes in GFP⁺ cells relative to Epcam⁺ cells. The Atf4 regulon is composed of 16 genes and the comparison of the regulon genes with detectable expression is shown. Relative expression ratios are shown as log₂FC values. e VIPER scores of differentially expressed transcription factors in each cluster. The data matrix was sorted by hierarchical clustering (complete linkage method) on both axes and represented as a heatmap. Transcription factors upregulated in the c1 cluster are indicated in red.