Sensing of extracellular L-Proline availability by the integrated stress response determines the outcome of cell competition

To address the mechanism by which ATF4 determines the outcome of cell competition, we performed transcriptomic comparisons by bulk RNA-seq analysis of up-regulated, down-regulated and background genes related to the DE analysis of homogenous cultures of Atf4-/- versus wild-type mouse ES cells and of p53-/-; Atf4-/- versus p53-/- mouse ES cells at day 3 of differentiation. Differential cellular pathway analysis by KEGG enrichment revealed that the topmost downregulated pathways in both sets of cells with Atf4 mutations were those associated with non-essential amino acid biosynthesis, transport and metabolism