c-MYC and p53 suppression restore Lgr5 ^high ISC proliferation in URI ^(Δ/Δ)Int mice. (A) qRT-PCR of Rspo1 and Rspo3 mRNA levels of URI^(+/+)Int; c-MYC^(+/+)Int; p53^(+/+)Int, URI^(Δ/Δ)Int; c-MYC^(+/+)Int; p53^(+/+)Int and URI^(Δ/Δ)Int; c-MYC^(Δ/Δ)Int; p53^(Δ/Δ)Int mice (n = 3). (B) qRT-PCR of Wnt3a mRNA levels of URI^(+/+)Int; c-MYC^(+/+)Int; p53^(+/+)Int, URI^(Δ/Δ)Int; c-MYC^(+/+)Int; p53^(+/+)Int, URI^(Δ/Δ)Int; c-MYC^(Δ/Δ)Int; p53^(Δ/Δ)Int, URI^(Δ/Δ)Int; c-MYC^(Δ/Δ)Int; p53^(+/+)Int, and URI^(Δ/Δ)Int; c-MYC^(+/+)Int; p53^(Δ/Δ)Int mice (n = 3). (C) Pictures represent crypt images before (with dots) and after (white/empty space) laser microdissection. Blue dots represent the exact point in which the laser impacts during tissue microdissection. The green line delineates the bottom part of the crypt. The red line delineates the upper part of the crypt. (D) qRT-PCR of Lgr5 mRNA levels in laser microdissected upper and basal parts of the crypt from URI^(+/+)Int mice. (E–G) qRT-PCR of Mki67 and AurkB (E), of Ascl2 and Olfm4 (F), and of Gfi1 and Hes1 (G) of laser microdissected upper parts of the crypts (Lgr5^low cells) from URI^(+/+)Int, URI^(Δ/Δ)Int, and URI^(Δ/Δ)Int; c-MYC^(Δ/Δ)Int; p53^(Δ/Δ)Int mice (n = 4). (H and I) qRT-PCR of Mki67 and AurkB (H) and Axin2 and Ascl2 (I) of laser microdissected basal part of the crypts (Lgr5^high cells) from URI^(+/+)Int, URI^(Δ/Δ)Int, and URI^(Δ/Δ)Int; c-MYC^(Δ/Δ)Int; p53^(Δ/Δ)Int mice (n = 4). Data represent mean ± SEM; *, P < 0.05; **, P < 0.01; and ***, P < 0.001; Student’s t test and one-way ANOVA. Scale bar represents 10 μm in C.