Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells

Publication date: 14 March 2017
Source:Cell Reports, Volume 18, Issue 11
Author(s): Kodandaramireddy Nalapareddy, Kalpana J. Nattamai, Rupali S. Kumar, Rebekah Karns, Kathryn A. Wikenheiser-Brokamp, Leesa L. Sampson, Maxime M. Mahe, Nambirajan Sundaram, Mary-Beth Yacyshyn, Bruce Yacyshyn, Michael A. Helmrath, Yi Zheng, Hartmut Geiger
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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Teaser

Nalapareddy et al. find that the decline of canonical Wnt signaling in intestinal stem cells (ISCs) leads to decreased ISC regenerative potential upon aging. Addition of exogenous Wnts in vitro improves regeneration of aged ISCs.


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