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Publication : Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells.

First Author  Nalapareddy K Year  2017
Journal  Cell Rep Volume  18
Issue  11 Pages  2608-2621
PubMed ID  28297666 Mgi Jnum  J:256193
Mgi Id  MGI:6103466 Doi  10.1016/j.celrep.2017.02.056
Citation  Nalapareddy K, et al. (2017) Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells. Cell Rep 18(11):2608-2621
abstractText  Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay. Our data demonstrate a role for impaired Wnt signaling in physiological aging of ISCs and further identify potential therapeutic avenues to improve ISC regenerative potential upon aging.
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