Mutual reinforcement between telomere capping and canonical Wnt signalling in the intestinal stem cell niche.

ABSTRACT: Critical telomere shortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis congenita) causes tissue pathology, but underlying mechanisms are not fully understood. Mice lacking telomerase (for example, mTR^-/- telomerase RNA template mutants) provide a model for investigating pathogenesis. In such mice, after several generations of telomerase deficiency telomeres shorten to the point of uncapping, causing defects most pronounced in high-turnover tissues including intestinal epithelium. Here we show that late-generation mTR^-/- mutants experience marked downregulation of Wnt pathway genes in intestinal crypt epithelia, including crypt base columnar stem cells and Paneth cells, and in underlying stroma. The importance of these ch

SUBMITTER: Yang TB 

PROVIDER: S-EPMC5357864 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature