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

Ting-Lin B. Yang, Qijun Chen, Jennifer T. Deng, Geetha Jagannathan, John W. Tobias, David C. Schultz, Shan Wang, Christopher J. Lengner, Anil K. Rustgi, John P. Lynch and F. Brad Johnson ()
Additional contact information
Ting-Lin B. Yang: Perelman School of Medicine, University of Pennsylvania
Qijun Chen: Perelman School of Medicine, University of Pennsylvania
Jennifer T. Deng: Perelman School of Medicine, University of Pennsylvania
Geetha Jagannathan: Perelman School of Medicine, University of Pennsylvania
John W. Tobias: Penn Molecular Profiling Center, Perelman School of Medicine, University of Pennsylvania
David C. Schultz: Wistar Institute, University of Pennsylvania
Shan Wang: School of Veterinary Medicine, University of Pennsylvania
Christopher J. Lengner: School of Veterinary Medicine, University of Pennsylvania
Anil K. Rustgi: Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
John P. Lynch: Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania
F. Brad Johnson: Perelman School of Medicine, University of Pennsylvania

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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 changes was revealed by rescue of crypt apoptosis and Wnt pathway gene expression upon treatment with Wnt pathway agonists. Rescue was associated with reduced telomere-dysfunction-induced foci and anaphase bridges, indicating improved telomere capping. Thus a mutually reinforcing feedback loop exists between telomere capping and Wnt signalling, and telomere capping can be impacted by extracellular cues in a fashion independent of telomerase.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms14766 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14766

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms14766

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().