经典Wnt信号通路可改善肠道干细胞衰老。
Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells.
作者信息
Nalapareddy Kodandaramireddy, Nattamai Kalpana J, Kumar Rupali S, Karns Rebekah, Wikenheiser-Brokamp Kathryn A, Sampson Leesa L, Mahe Maxime M, Sundaram Nambirajan, Yacyshyn Mary-Beth, Yacyshyn Bruce, Helmrath Michael A, Zheng Yi, Geiger Hartmut
机构信息
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA.
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH 45229, USA.
出版信息
Cell Rep. 2017 Mar 14;18(11):2608-2621. doi: 10.1016/j.celrep.2017.02.056.
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.
尽管肠道稳态由肠道干细胞（ISC）维持，但衰老时再生能力受损。在此，我们首先揭示衰老时肠道结构、细胞数量和细胞组成的变化。其次，我们确定衰老时ISC的再生能力下降是由于ISC中经典Wnt信号通路的下降。Wnt表达的变化在干细胞本身及其微环境中被发现，包括潘氏细胞和间充质。第三，重新激活经典Wnt信号通路可增强小鼠和人类ISC的功能，因此，在类器官试验中改善了ISC与衰老相关的表型。我们的数据证明了Wnt信号通路受损在ISC生理衰老中的作用，并进一步确定了改善衰老时ISC再生潜力的潜在治疗途径。
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