Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells

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

doi:10.1016/j.celrep.2017.02.056

Cell Reports (Mar 2017)

Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells

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

Affiliations

Kodandaramireddy Nalapareddy: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Kalpana J. Nattamai: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Rupali S. Kumar: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Rebekah Karns: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Kathryn A. Wikenheiser-Brokamp: Divisions of Pathology and Laboratory Medicine and Pulmonary Biology, Perinatal Institute, Cincinnati Children’s Hospital Medical Center and Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45229, USA
Leesa L. Sampson: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Maxime M. Mahe: Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Nambirajan Sundaram: Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Mary-Beth Yacyshyn: Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH 45229, USA
Bruce Yacyshyn: Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH 45229, USA
Michael A. Helmrath: Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Yi Zheng: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA
Hartmut Geiger: Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA

DOI: https://doi.org/10.1016/j.celrep.2017.02.056
Journal volume & issue: Vol. 18, no. 11
pp. 2608 – 2621

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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