This study utilized a mouse model of LS, as described in the Methods and Figure 1A. To investigate the intrinsic transcriptomic changes induced by EZH2 inhibition with GSK503 (5 μM) in adenomatous polyps (AP) during tumorigenesis, we performed RNA-Seq analysis using mouse-derived organoids (MDOs) from large intestine AP (N = 2 controls, N = 3 treated) and adjacent normal colonic mucosa (NM; N = 3 controls, N = 3 treated) from VCMsh2THu mice. Here, EZH2 is linked to Leigh syndrome.