(a) Representative images showing apoptotic changes by TUNEL staining in intestinal crypts of G4 mTR−/− mice treated for 8 days with subcutaneous injections of R-spondin1 (Rspo1) (n=4 Rspo1-treated and 5 littermate controls). Scale bars, 50 μm. (b) Representative image showing Ascl2 transcripts differences in Rspo1-treated and control G4 mTR−/− mice (n=3). Scale bars, 100 μm. (c) Representative images showing Sox9 protein differences in Rspo1-treated and control G4 mTR−/− mice (n=4 control and 3 Rspo1-treated). Scale bars, 50 μm. (d) Representative images showing reduced telomere dysfunction as measured by anaphase bridges in Rspo1-treated G4 mTR−/− mice (left, untreated; middle, Rspo1-treated). Quantitation of anaphase bridges (right). 120 crypts per mouse from 5 control G4 mice and 4 Rspo1-treated G4 mice were surveyed for anaphase bridges. Scale bars, 10 μm. (e) Representative images and quantitation (right) showing reduced telomere dysfunction as measured by TIFs in Rspo1-treated G4 mTR−/− mice (n=3). Scale bars, 5 μm. All error bars reflect s.e.m., and P values reflect unpaired two-tailed Student's t-tests, with *P<0.05, **P<0.005 and *** P<0.0005.